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DEM2016 | Lysosomal recruitment of TSC2 is a universal response to cellular stress | Demetriades C; Teleman AA et al. | 2,016 | Nature communications | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1038/ncomms10662 | 26,868,506 | PMC4754342 | Lysosomal recruitment of TSC2 is a universal response to cellular stress that inhibits mTORC1.
| mTORC1 promotes cell growth and is therefore inactivated upon unfavourable growth conditions. Signalling pathways downstream of most cellular stresses converge on TSC1/2, which serves as an integration point that inhibits mTORC1. The TSC1/2 complex was shown to translocate to lysosomes to inactivate mTORC1 in response ... | Various cellular stresses (amino-acid/growth-factor withdrawal, etc.) – mechanistic | TSC2 / mTORC1 | Mammalian cells | Diverse stresses relocate TSC2 to the lysosome → inhibit mTORC1 (a universal response) | null | null | null | null | https://mtor-atlas.org/study/DEM2016/ |
INOK2003 | Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling | Inoki K; Guan KL et al. | 2,003 | Genes & development | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | In vitro; Drosophila | Yes | 10.1101/gad.1110003 | 12,869,586 | PMC196227 | TSC2 is a GAP for Rheb; loss of TSC2 raises Rheb-GTP and constitutively activates mTOR.
| Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP)... | Biochemical/genetic (TSC2 GAP activity toward Rheb) | Rheb / TSC2 / mTOR | In vitro; Drosophila | TSC2 is a GAP for Rheb; Rheb-GTP activates mTOR/S6K/4EBP1 (rapamycin-sensitive) | null | null | null | null | https://mtor-atlas.org/study/INOK2003/ |
INO2002 | TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling | Inoki K; Guan KL et al. | 2,002 | Nature Cell Biology | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human cell lines | Yes | 10.1038/ncb839 | 12,172,553 | null | Akt directly phosphorylates and inactivates TSC2, disrupting the TSC1-TSC2 complex and releasing its inhibition of mTOR - the link between growth-factor/insulin signaling and mTORC1 activation.
| Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by the formation of hamartomas in a wide range of human tissues. Mutation in either the TSC1 or TSC2 tumour suppressor gene is responsible for both the familial and sporadic forms of this disease. TSC1 and TSC2 proteins form a physical and functio... | Biochemical/genetic (Akt phosphorylation of TSC2) | TSC2 / Akt / mTOR | Human cell lines | Akt phosphorylates and inactivates TSC2 → relieves mTOR inhibition (links insulin/growth factors to mTORC1) | null | null | null | null | https://mtor-atlas.org/study/INO2002/ |
YU2026 | High-concentration hydrogen mitigates cognitive impairment in a murine model of Sepsis-associated encephalopathy by enhancing oligodendrocyte maturation and myelination in the mPFC | Yu J; Qi W; Li F; Chang B; Wang Zengkun; Kan Y; Yu Yonghao; Yu Yang | 2,026 | Progress in Neuro-Psychopharmacology and Biological Psychiatry | C - Animal | 4 - Animal Study | Animal | Mouse (CLP-induced SAE model) | Yes | 10.1016/j.pnpbp.2026.111892 | null | null | In a mouse model of sepsis-associated encephalopathy (SAE), mTOR hyperactivation impairs oligodendrocyte maturation and causes cognitive deficits; hydrogen gas and rapamycin suppress mTOR, restore myelination, and improve cognition in these mice.
| Sepsis-associated encephalopathy (SAE) commonly elicits long-lasting cognitive deterioration. This study investigates whether high-concentration (67%) hydrogen gas protects against SAE by promoting oligodendrocyte maturation and myelination in the medial prefrontal cortex (mPFC). mTOR hyperactivation in the mPFC of SAE... | 67% Hydrogen gas; Rapamycin; NV-5138 (mTOR agonist) | mTOR pathway; oligodendrocyte precursor cell differentiation; myelination | Mouse | In mice, mTOR hyperactivation blocks OPC differentiation and myelination causing cognitive decline; hydrogen + rapamycin suppress mTOR and restore cognition | null | null | null | null | https://mtor-atlas.org/study/YU2026/ |
JIN2026B | Rapamycin attenuates age-related atrial remodeling and fibrillation by targeting HIF-1α-mediated metabolic dysregulation. | Jin L; Jiang T; Gong H et al. | 2,026 | Biochimica et Biophysica Acta - Molecular Basis of Disease | C - Animal | 4 - Animal Study | Animal | Mouse (D-galactose aging model) | Yes | 10.1016/j.bbadis.2026.168438 | null | null | Dietary rapamycin reduced aging-induced atrial fibrillation susceptibility and atrial remodelling in D-galactose-aged mice, acting through mTOR-independent inhibition of HIF-1α plus restored mitochondrial function and insulin sensitivity.
| Atrial fibrillation (AF) is an age-related disease. Although rapamycin is a foremost anti-aging therapy with proven efficacy in lifespan extension, its impact on aging-induced atrial remodeling and AF susceptibility was unknown. An aging-induced AF-susceptible mouse model was produced by D-galactose injection followed ... | Rapamycin (dietary) | HIF-1α (mTOR-independent); mitochondrial metabolism | Mouse | Reduced AF susceptibility, improved insulin resistance, restored mitochondrial function and substrate utilisation | null | null | null | null | https://mtor-atlas.org/study/JIN2026B/ |
LOF2011 | Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop | Löffler AS et al. | 2,011 | Autophagy | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human cells; mouse | Yes | 10.4161/auto.7.7.15451 | 21,460,634 | null | ULK1 phosphorylates and inhibits AMPK in return, showing autophagy signaling is a bidirectional feedback loop, not a one-way switch.
| Unc-51-like kinase 1 (Ulk1) plays a central role in autophagy induction. It forms a stable complex with Atg13 and focal adhesion kinase (FAK) family interacting protein of 200 kDa (FIP 200). This complex is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1) in a nutrient-dependent way. AMP-act... | Biochemical (ULK1–AMPK) | ULK1 / AMPK / mTORC1 | Human cells; mouse | ULK1 phosphorylates and inhibits AMPK – a negative feedback loop in autophagy signaling | null | null | null | null | https://mtor-atlas.org/study/LOF2011/ |
KIM2003 | GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR | Kim DH; Sarbassov DD; Ali SM; Latek RR; Guntur KVP; Erdjument-Bromage H; Tempst P; Sabatini DM | 2,003 | Molecular Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human cells (biochemistry) | Yes | 10.1016/s1097-2765(03)00114-x | 12,718,876 | null | Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex.
| mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors. Here, we identify a member of this pathway, a protein named GbetaL that binds to the kinase domain of mTOR and stabilizes the interaction of raptor with mTOR. Like mTOR and raptor, Gbe... | Biochemical – identification of GβL (mLST8) | mTOR / raptor / GβL (mLST8) | Human cells (biochemistry) | GβL binds the mTOR kinase domain and stabilizes the raptor–mTOR interaction; stimulates nutrient-sensitive signaling to S6K1 and cell-size control | null | null | null | null | https://mtor-atlas.org/study/KIM2003/ |
JIN2026C | Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice | Jin N; Zhou L; Gui H; Tang J; Huang X; Wang W; Jin G; Cheng H; Liang Y; Geng X; Peng Z; Zhao H; Liu Z; Xie J | 2,026 | Aging Cell | C - Animal | 4 - Animal Study | Animal | Aged (80-90 wk) male Ldlr-/- mice with established atherosclerosis; rapamycin i.p. triweekly x 8 weeks vs. control | Yes | 10.1111/acel.70720 | 42,775,680 | null | In aged atherosclerotic mice, rapamycin (mTORC1 inhibition) reduced plaque macrophage content and total T cell numbers, shifted CD8 T cells from effector to central-memory phenotype, enriched aortic regulatory T cells (higher Foxp3/Tgfb1), reduced Tfh cells, germinal-center B cells, plasma cells and autoantibody levels... | Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was i... | null | null | null | null | null | null | null | null | https://mtor-atlas.org/study/JIN2026C/ |
LIS2026 | Notoginsenoside R1 Alleviates Acetaminophen-Induced Liver Injury via MAPK/mTOR-Mediated Autophagy. | Li S, Liu Z, Pan G, Li Y, Lv K | 2,026 | The American Journal of Chinese Medicine | C - Animal | 4 - Animal Study | Animal | Mouse | Yes | 10.1142/S0192415X26500576 | 42,459,050 | null | Notoginsenoside R1 alleviates acetaminophen-induced acute liver injury by activating protective autophagy through MAPK/mTOR pathway modulation, reducing hepatocyte death and oxidative damage.
| Notoginsenoside R1 (NGR1), a bioactive saponin from Panax notoginseng, was investigated in acetaminophen-induced acute liver injury (AILI). NGR1 treatment activated autophagy via modulation of the MAPK/mTOR pathway, reducing hepatocyte apoptosis and oxidative stress, and attenuating liver injury in mouse models and hep... | Notoginsenoside R1 | MAPK/mTOR pathway; autophagy | Mouse | NGR1 suppresses mTOR to activate autophagy, reducing APAP-induced hepatocyte apoptosis and liver injury | null | null | null | null | https://mtor-atlas.org/study/LIS2026/ |
GWI2008 | AMPK phosphorylation of raptor mediates a metabolic checkpoint | Gwinn DM; Shackelford DB; Egan DF; Mihaylova MM; Mery A; Vasquez DS; Turk BE; Shaw RJ | 2,008 | Molecular Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human/mouse cells (biochemistry) | Yes | 10.1016/j.molcel.2008.03.003 | 18,439,900 | PMC2674027 | Found a SECOND way the energy sensor AMPK shuts mTORC1 down. Besides acting through TSC2, AMPK directly phosphorylates Raptor - the core mTORC1 subunit - to halt growth when energy runs low. This 'metabolic checkpoint' is exactly the switch that drugs like metformin and exercise tap into.
| AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC2... | Biochemical/genetic (AMPK phosphorylation of raptor) | raptor / mTORC1 / AMPK | Human/mouse cells (biochemistry) | Under energy stress AMPK phosphorylates raptor → a metabolic checkpoint that suppresses mTORC1 | null | null | null | null | https://mtor-atlas.org/study/GWI2008/ |
VITTE2026 | Efficacy and safety of everolimus in heart transplant recipients: A meta-analysis | Vitte SH; Luna AM; Pille JJ; Pinheiro BN; Souza MBL; Irudhayaraj CDJ; Munaretto GM | 2,026 | JHLT Open | A - Systematic review | 1 - Systematic Review | Human | Human (adult and paediatric heart transplant recipients) | Yes | 10.1016/j.jhlto.2026.100610 | 42,656,203 | PMC13506258 | Meta-analysis of 60 studies (1786 heart transplant recipients): everolimus-based immunosuppression reduced cardiac allograft vasculopathy progression on IVUS (RR ~0.57) and preserved renal function (eGFR +10-15 mL/min) when combined with calcineurin-inhibitor minimisation, with neutral all-cause mortality (RR ~0.98) bu... | Long-term outcomes after heart transplantation remain limited by cardiac allograft vasculopathy (CAV) and calcineurin inhibitor (CNI)-related nephrotoxicity. Everolimus has emerged as a CNI-sparing strategy, yet its net clinical benefit remains debated. To determine whether everolimus-based immunosuppression improves e... | Everolimus-based immunosuppression (with calcineurin-inhibitor minimisation or withdrawal) vs standard CNI-based therapy | mTORC1 (everolimus) | Human | Reduced cardiac allograft vasculopathy progression and better renal function; mortality neutral; more adverse events and discontinuations | null | null | null | null | https://mtor-atlas.org/study/VITTE2026/ |
VIL2021 | mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis | Villa E; Sahu U; O'Hara BP; Ali ES; Helmin KA; Asara JM; Gao P; Singer BD; Ben-Sahra I | 2,021 | Molecular Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human cells; mouse xenograft tumors | Yes | 10.1016/j.molcel.2021.03.009 | 33,756,106 | PMC8141029 | SAMTOR (GU2017) showed the cell can sense S-adenosylmethionine and report it to mTORC1. This study runs the arrow the other way: mTORC1 controls how much SAM the cell makes. Downstream of mTORC1, c-MYC binds intron 1 of MAT2A and raises expression of the enzyme that produces SAM, the cell's main methyl donor; mTORC1 se... | The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient, growth, and oncogenic signals. We found that mTORC1 stimulates the synthesis of the major methyl donor, S-adenosylmethionine (SAM), through the control of methionine adenosyltransferase 2 alpha (MAT2A) e... | Genetic/pharmacologic (mTORC1, MAT2A inhibition) | mTORC1 / c-MYC / MAT2A / SAM / WTAP / m6A | Human cells; mouse xenograft tumors | mTORC1 raises SAM production and WTAP levels, increasing m6A mRNA modification and protein synthesis to support cell growth | null | null | null | null | https://mtor-atlas.org/study/VIL2021/ |
DEOLIVEIRA2026 | Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16 oncogene expression in breast cancer. | de Oliveira Isidio BE; Fontes PHB; da Silva GRP; Leao SL; de Franca Sao Marcos B; et al. | 2,026 | Exploration of targeted anti-tumor therapy | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human (clinical samples, FFPE tissue) | Yes | 10.37349/etat.2026.1002391 | 42,558,973 | PMC13439120 | In breast tumour tissue (48 of 92 patients with usable RNA), HPV16 oncogene expression was associated with higher PI3K and lower mTOR transcript levels. The design is correlational and measures mRNA only, so it does not show that the virus activates the mTOR pathway.
| Breast cancer is the most prevalent malignant tumor among women. Human papillomavirus (HPV) has been detected in breast tumors since the 1990s, and beyond its oncogenic potential, therapy resistance driven by viral immune evasion in non-anogenital tumors, such as oropharyngeal cancers, highlights the need to investigat... | HPV16 oncogene expression | PI3K/AKT/mTOR | Human | HPV-positive tumours: PI3K mRNA higher, mTOR mRNA lower (association) | null | null | null | null | https://mtor-atlas.org/study/DEOLIVEIRA2026/ |
SIL2026 | Enforcing mTORC1 activity in therapeutic CD4+ T cells promotes persistence but eventual immune exhaustion | Sillito F; Armbrecht E; O'Neill AT; McIntyre A; Nyatondo M; Holler A; Callender LA; Henson SM; Stauss H; Chakraverty R | 2,026 | Journal of Immunology | C - Animal | 4 - Animal Study | Mechanism | Mouse CD4+ T cells, adoptive transfer tumor model | Yes | 10.1093/jimmun/vkag206 | 42,566,506 | null | Enforced RHEB overexpression (mTORC1 hyperactivation) in therapeutic CD4+ T cells boosts initial proliferation/persistence after adoptive transfer, but drives cells toward an exhausted phenotype (co-inhibitory receptors, impaired re-proliferation on rechallenge) -- a double-edged sword for CAR/TCR-T cell engineering, d... | There is substantial interest in developing novel engineering strategies to promote the sustained metabolic fitness of therapeutic T cells. We previously showed that overexpression of RAS homologue enriched in brain (RHEB), a positive regulator of mammalian target of rapamycin complex 1 (mTORC1), promotes aerobic glyco... | null | Rheb / mTORC1 | null | null | null | null | null | null | https://mtor-atlas.org/study/SIL2026/ |
BRO1996 | Dwarf mice and the ageing process | Brown-Borg HM; Bartke A et al. | 1,996 | Nature | C - Animal | 4 - Animal Study | Animal | Ames dwarf mice (growth-hormone deficient) | Yes | 10.1038/384033a0 | 8,900,272 | null | Mice with growth hormone deficiency lived substantially longer than normal littermates - founding observation linking reduced growth-signaling to mammalian longevity.
| (Brief communication; no formal abstract in PubMed — editorial summary.) This landmark report shows that Ames dwarf mice, which carry a mutation causing combined deficiency of growth hormone, prolactin and thyroid-stimulating hormone, live substantially longer than their normal littermates (both sexes). It was among th... | Genetic – Ames dwarf mutation (GH/prolactin/TSH deficiency) | GH/IGF-1 axis (upstream of PI3K-Akt-mTOR) | Mouse (Ames dwarf) | Substantially longer lifespan vs normal littermates (both sexes) – early evidence linking reduced growth signaling to longevity | null | null | null | null | https://mtor-atlas.org/study/BRO1996/ |
KOR2011 | Lysosomal positioning coordinates cellular nutrient responses | Korolchuk VI; Saiki S; Lichtenberg M; Siddiqi FH; Roberts EA; Imarisio S; Jahreiss L; Sarkar S; Futter M; Menzies FM; O'Kane CJ; Deretic V; Rubinsztein DC | 2,011 | Nature cell biology | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1038/ncb2204 | 21,394,080 | null | Where the lysosome sits inside the cell helps decide whether mTORC1 is on. With nutrients available, lysosomes move to the cell periphery, physically close to the plasma-membrane signalling modules, and mTORC1 is active there; starvation changes intracellular pH and pulls lysosomes into a cluster around the nucleus, wh... | mTOR (mammalian target of rapamycin) signalling and macroautophagy (henceforth autophagy) regulate numerous pathological and physiological processes, including cellular responses to altered nutrient levels. However, the mechanisms regulating mTOR and autophagy remain incompletely understood. Lysosomes are dynamic intra... | null | null | null | null | null | null | null | null | https://mtor-atlas.org/study/KOR2011/ |
HSI2012 | The translational landscape of mTOR signalling steers cancer initiation and metastasis | Hsieh AC; Liu Yi; Edlind MP; Ingolia NT; Janes MR; Sher A; et al.; Ruggero D | 2,012 | Nature | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mouse models + human prostate cancer | Yes | 10.1038/nature10912 | 22,367,541 | PMC3663483 | Showed WHY mTOR-driven translation matters for cancer: in prostate cancer, oncogenic mTOR selectively translates a specific set of pro-invasion mRNAs that drive metastasis. An ATP-competitive mTOR inhibitor (INK128) reversed that signature - an early preclinical rationale from mouse models and cell lines, not a clinica... | The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover... | Oncogenic mTOR modulation + ribosome profiling | mTOR / 4E-BP–eIF4E translation | Mouse models + human prostate cancer | Oncogenic mTOR reprograms translation of a specific gene set driving proliferation, metabolism and invasion/metastasis | null | null | null | null | https://mtor-atlas.org/study/HSI2012/ |
BOU2020 | AIMTOR, a BRET biosensor for live imaging, reveals subcellular mTOR signaling and dysfunctions | Bouquier N; Ollendorff V et al. | 2,020 | BMC Biology | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | HEK293 cells; primary hippocampal neurons and muscle cells (mouse); biosensor tool | Yes | 10.1186/s12915-020-00790-8 | 32,620,110 | PMC7334845 | AIMTOR is a genetically encoded BRET biosensor that reads out mTOR activity live in single cells and in specific subcellular compartments (cytosol, lysosome surface, nucleus, near mitochondria).
| mTOR signaling is an essential nutrient and energetic sensing pathway. Here we describe AIMTOR, a sensitive genetically encoded BRET (Bioluminescent Resonance Energy Transfer) biosensor to study mTOR activity in living cells. As a proof of principle, we show in both cell lines and primary cell cultures that AIMTOR BRET... | Genetically encoded BRET biosensor (AIMTOR) -- tool, not a drug intervention | mTOR activity (live, subcellular) | Human (HEK293); mouse (neurons, muscle) | Enables real-time single-cell/subcellular measurement of mTOR activity dynamics | null | null | null | null | https://mtor-atlas.org/study/BOU2020/ |
CHEN2026C | Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation | Chen Xianglong; Gao H; Wu W; Shi P; Chen Yuhang; Zhang A; Cheng Z; Wu W; Yu Z; Zhang Y | 2,026 | Advanced Science | C - Animal | 4 - Animal Study | Mechanism | Human nucleus pulposus cells; rat caudal needle-puncture model | Yes | 10.1002/advs.77428 | 42,658,647 | null | Loss of chaperone-mediated autophagy lets its substrate midnolin (MIDN) accumulate; MIDN binds TSC2 and drives its proteasomal degradation independently of ubiquitination, de-repressing mTORC1 and causing senescence, SASP and matrix loss in disc cells. MIDN knockdown, LAMP2A overexpression or rapamycin each blocked the... | Intervertebral disc degeneration (IDD) is a leading cause of low back pain with incompletely understood mechanisms. Although autophagy dysfunction is a documented contributor to IDD, the precise pathobiological role of chaperone-mediated autophagy (CMA) remains poorly understood. Here, we demonstrate that CMA activity ... | MIDN knockdown (shRNA), LAMP2A overexpression (CMA activation), rapamycin | TSC2 / mTORC1 (via midnolin, MIDN) | Human cells; rat | Impaired CMA -> MIDN accumulation -> TSC2 degradation -> mTORC1 hyperactivation -> senescence, SASP and matrix loss; blocked by MIDN knockdown, LAMP2A overexpression or rapamycin | null | null | null | null | https://mtor-atlas.org/study/CHEN2026C/ |
JAC2006 | SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity | Jacinto E; Su B et al. | 2,006 | Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1016/j.cell.2006.08.033 | 16,962,653 | null | SIN1 maintains rictor-mTOR integrity and confers mTORC2 Akt-Ser473 kinase activity and substrate specificity.
| Mammalian target of rapamycin (mTOR) controls cell growth and proliferation via the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes. Recent biochemical studies suggested that TORC2 is the elusive PDK2 for Akt/PKB Ser473 phosphorylation in the hydrophobic motif. Phosphorylation at Ser473, along with Thr308... | Biochemical/genetic (SIN1/MIP1) | mTORC2 (rictor-mTOR) / Akt Ser473 | Mammalian cells | SIN1 maintains rictor–mTOR (mTORC2) integrity and controls Akt Ser473 phosphorylation and substrate specificity | null | null | null | null | https://mtor-atlas.org/study/JAC2006/ |
BOB2026 | mTOR signaling in aging: from causality to geroprotective interventions and hallmark-level outcomes | Bobok N | 2,026 | Aging (Albany NY) | D - Mechanistic/Review | Narrative Review | Review | Narrative review synthesis (model organisms + human associative data) | Yes | 10.18632/aging.206423 | 42,765,942 | null | Frames mTOR as a dynamic, context-dependent signaling hub integrating nutrient sensing, proteostasis, autophagy and stress adaptation across the hallmarks of aging; surveys geroprotective interventions (autophagy activation, dietary restriction, exercise, senotherapeutics) that partly converge on mTOR signaling. Causal... | The mechanistic target of rapamycin (mTOR) pathway is an important integrator of processes involved in aging and longevity, coordinating nutrient sensing, metabolic adaptation, and cellular stress responses. This review presents a three-section framework in which mTOR functions as a dynamic signaling hub coordinating m... | null | null | null | null | null | null | null | null | https://mtor-atlas.org/study/BOB2026/ |
ALI2020 | ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis | Ali ES; Sahu U; Villa E; O'Hara BP; Gao P; Beaudet C; Wood AW; Asara JM; Ben-Sahra I | 2,020 | Molecular Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human cancer cells; tumor | Yes | 10.1016/j.molcel.2020.05.001 | 32,485,148 | PMC7306006 | The Atlas records several routes by which mTORC1 drives purine synthesis. This study shows mTORC1 is not the only growth pathway with that power: RAS-ERK signalling stimulates purine synthesis directly and within minutes, because ERK2 - but not ERK1 - phosphorylates the purine synthesis enzyme PFAS at Thr619. Cells exp... | The RAS-ERK/MAPK (RAS-extracellular signal-regulated kinase/mitogen-activated protein kinase) pathway integrates growth-promoting signals to stimulate cell growth and proliferation, at least in part, through alterations in metabolic gene expression. However, examples of direct and rapid regulation of the metabolic path... | Genetic (PFAS T619A); ERK pathway activation | RAS / ERK2 / PFAS (de novo purine synthesis) | Human cancer cells; mouse tumors | ERK2 phosphorylates PFAS at T619 to stimulate de novo purine synthesis, supporting cell proliferation and tumor growth | null | null | null | null | https://mtor-atlas.org/study/ALI2020/ |
CHI2012 | Regulation and function of mTOR signalling in T cell fate decisions | Chi H | 2,012 | Nature reviews. Immunology | D - Mechanistic/Review | Narrative Review | Review | Review | Yes | 10.1038/nri3198 | 22,517,423 | PMC3417069 | Review of mTOR signalling in T-cell fate decisions.
| The evolutionarily conserved kinase mTOR (mammalian target of rapamycin) couples cell growth and metabolism to environmental inputs in eukaryotes. T cells depend on mTOR signalling to integrate immune signals and metabolic cues for their proper maintenance and activation. Under steady-state conditions, mTOR is actively... | Not applicable (review) | mTOR / mTORC1 & mTORC2 | Review | mTOR integrates immune and metabolic cues to program T-cell homeostasis, activation and differentiation | null | null | null | null | https://mtor-atlas.org/study/CHI2012/ |
CHEN2026 | FGF21-modified adipose stem cell-derived exosomes promote wound healing by activating fibroblast glycolysis through AMPK/mTOR signaling. | Chen K; Chen X; Wen C; Chen W; Liao Z; et al. | 2,026 | Cellular signalling | C - Animal | 4 - Animal Study | Mechanism | Mouse + Human fibroblasts | Yes | 10.1016/j.cellsig.2026.112742 | 42,551,612 | null | FGF21-enriched exosomes from engineered ADSCs promote chronic wound healing by activating fibroblast glycolysis via AMPK/mTOR signaling, improving proliferation, migration, and tissue repair in a mouse model.
| Chronic wound healing disorders remain a significant clinical challenge, largely due to the limited effectiveness of conventional therapeutic strategies. Emerging evidence suggests that engineered exosomes represent a promising cell-free therapeutic approach. This study aimed to elucidate the mechanisms by which FGF21-... | FGF21-modified ADSC exosomes | AMPK/mTOR | Mouse + Human (fibroblasts in vitro) | Promotes wound healing via AMPK/mTOR-activated glycolysis in fibroblasts | null | null | null | null | https://mtor-atlas.org/study/CHEN2026/ |
KRA2018 | A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort | Kraig E; Linehan LA; Liang H; Romo TQ; Liu Q; et al.; Kellogg DL | 2,018 | Experimental Gerontology | B - Human | 2 - Human Clinical Trial | Human | Humans, pilot RCT (n=25, ages 70-95) | Yes | 10.1016/j.exger.2017.12.026 | 29,408,453 | PMC5869166 | A safety-first pilot RCT (n=25, ages 70-95) asking the basic question before any longevity trial: is daily rapamycin safe in healthy older people? Over 8+ weeks it was well tolerated with only minor red-blood-cell changes and - importantly - NO rise in blood glucose or insulin resistance in this short window. Groundwor... | Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that... | Rapamycin (oral, daily, ~8 weeks) | mTOR / mTORC1 | Human – healthy older adults (age 70–95, n=25) | Well tolerated; NO rise in blood glucose / insulin resistance in the short window – groundwork for larger geroprotection trials | Rapamycin 1 mg daily orally (single dose tested; blood levels monitored in first 4 subjects), ~8-16 weeks; placebo-controlled. | n=25 randomised (11 rapamycin, 14 placebo analysed); healthy older adults aged 70-95. | Established feasibility and safety of daily low-dose rapamycin in older adults; no serious adverse events; groundwork for larger geroprotection trials. | Small sample -> single 1 mg dose chosen; short duration; feasibility (not efficacy) study. | https://mtor-atlas.org/study/KRA2018/ |
XIA2026 | Nutrient-sensing pathways in adult stem cells: Orchestrating homeostasis, aging, and disease | Xiao T; Zeng YA; Hu C et al. | 2,026 | Seminars in Cell & Developmental Biology | D - Mechanistic/Review | Narrative Review | Review | Review (adult stem cells, multiple tissue systems) | Yes | 10.1016/j.semcdb.2026.103690 | 42,546,460 | null | Proposes an integrated framework in which mTOR, AMPK, sirtuins, and insulin/IGF-1 signaling jointly govern adult stem cell transitions between quiescence, activation, and differentiation; age-related dysregulation of this nutrient-sensing network drives stem cell exhaustion and tissue degeneration, and interventions (m... | Nutrient-sensing pathways, including mTOR, AMPK, Sirtuins, and insulin/IGF-1 signaling, are central regulators orchestrating adult stem cell (ASC) fate by dynamically modulating cellular metabolism. This review proposes a framework that integrates these pathways into a cohesive network that dictates the metabolic trans... | N/A (review); discusses mTOR inhibitors, AMPK activators, NAD+ precursors, dietary strategies as ASC-rejuvenating interventions | mTOR / AMPK / Sirtuins / IGF-1 nutrient-sensing network | Review (multiple species/systems) | Integrated nutrient-sensing network governs adult stem cell quiescence/activation/differentiation; dysregulation drives stem cell exhaustion and aging | null | null | null | null | https://mtor-atlas.org/study/XIA2026/ |
MAX2009 | Molecular mechanisms of mTOR-mediated translational control | Ma XM; Blenis J et al. | 2,009 | Nature reviews. Molecular cell biology | D - Mechanistic/Review | Narrative Review | Review | Review | Yes | 10.1038/nrm2672 | 19,339,977 | null | Review of the molecular mechanisms of mTOR-mediated translational control.
| The process of translation requires substantial cellular resources. Cells have therefore evolved complex mechanisms to control overall protein synthesis as well as the translation of specific mRNAs that are crucial for cell growth and proliferation. At the heart of this process is the mammalian target of rapamycin (mTO... | Not applicable (review) | mTOR / 4E-BP / S6K translation machinery | Review | Reviews how mTOR senses nutrients/energy/hormones to control protein synthesis | null | null | null | null | https://mtor-atlas.org/study/MAX2009/ |
HEI1991 | Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast | Heitman J; Movva NR; Hall MN | 1,991 | Science | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Yeast (Saccharomyces cerevisiae) | Yes | 10.1126/science.1715094 | 1,715,094 | null | Discovery of the TOR1 and TOR2 genes in yeast as the targets whose disruption causes rapamycin's cell-cycle-arresting toxicity - the original genetic identification of the TOR pathway.
| FK506 and rapamycin are related immunosuppressive compounds that block helper T cell activation by interfering with signal transduction. In vitro, both drugs bind and inhibit the FK506-binding protein (FKBP) proline rotamase. Saccharomyces cerevisiae cells treated with rapamycin irreversibly arrested in the G1 phase of... | Rapamycin (FKBP-rapamycin); genetic (FPR1, TOR) | FKBP / TOR | Yeast (S. cerevisiae) | FKBP-rapamycin complex arrests cells in G1; identified FKBP and TOR as targets – a foundational discovery | null | null | null | null | https://mtor-atlas.org/study/HEI1991/ |
GAO2026 | Astragaloside IV Mitigates Tacrolimus-Induced Chronic Nephrotoxicity by Regulating the mTOR-TFEB-GADD45alpha Pathway | Ping Gao, Xinwei Cheng, Rui Xu, Xinyu Huang, Jianqiao Wang, Maochang Liu, Xiuxun Wu, Xinlei Guan, Yunzhou Chen, Zhenpeng Qiu | 2,026 | Journal of Agricultural and Food Chemistry | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | In vitro (renal cell lines) | Yes | 10.1021/acs.jafc.5c17921 | 42,438,242 | null | Astragaloside IV protects against tacrolimus-induced nephrotoxicity by inhibiting mTOR to activate TFEB and restore autophagy, nominating the mTOR-TFEB-GADD45alpha axis as a calcineurin-independent candidate therapeutic target (preclinical; no human data) in TICN.
| Tacrolimus-induced chronic nephrotoxicity (TICN) is mediated in part through calcineurin-dependent TFEB phosphorylation. Astragaloside IV (AS-IV) significantly reactivated TFEB and restored tacrolimus-impaired renal function, autophagy flux, and DNA repair. TFEB knockdown reversed AS-IV effects. AS-IV does not affect c... | Astragaloside IV | mTOR / TFEB / GADD45alpha / autophagy | In vitro (renal cells) | TFEB reactivation, restored autophagy flux, improved renal function markers, attenuation of nephrotoxicity | null | null | null | null | https://mtor-atlas.org/study/GAO2026/ |
FON2010 | Extending healthy life span--from yeast to humans | Fontana L; Partridge L; Longo VD | 2,010 | Science | D - Mechanistic/Review | Narrative Review | Review | Review (yeast to humans) | Yes | 10.1126/science.1172539 | 20,395,504 | PMC3607354 | Influential review proposing that dietary restriction and reduced nutrient-sensing signalling (mTOR, GH/IGF-1) may slow ageing through similar, evolutionarily conserved mechanisms. Lifespan extension is shown in yeast, invertebrates, rodents and rhesus monkeys; in humans the evidence is limited to protective biomarker ... | When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutr... | Not applicable (review – dietary restriction / nutrient-sensing inhibition) | Nutrient-sensing pathways (incl. TOR, insulin/IGF) | Review (yeast to humans) | Dietary restriction and reduced nutrient-sensing activity extend lifespan and reduce age-related disease | null | null | null | null | https://mtor-atlas.org/study/FON2010/ |
CAS2009 | mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging | Castilho RM; Gutkind JS et al. | 2,009 | Cell stem cell | C - Animal | 4 - Animal Study | Animal | Mouse | Yes | 10.1016/j.stem.2009.06.017 | 19,733,540 | PMC2939833 | Wnt-induced mTOR activation drives epidermal stem-cell senescence; rapamycin rescues it.
| Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent expr... | Wnt1 overexpression; rapamycin rescue | mTOR | Mouse (epidermal stem cells) | Wnt→mTOR drives stem-cell senescence/exhaustion and hair loss; rapamycin reverses it | not stated | n=25 mutant and wild-type littermates | Wnt1 expression caused terminal differentiation of HF after 90 days, leading to progressive hair loss. | No nuclear β-catenin staining could be observed, possibly due to strong membrane signal or limited nuclear β-catenin; further investigation is warranted on the contribution of particular Wnt1 receptors. | https://mtor-atlas.org/study/CAS2009/ |
SAC2011 | Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size | Saci A; Carpenter CL et al. | 2,011 | Molecular cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1016/j.molcel.2011.03.017 | 21,474,067 | PMC3750737 | Rac1 binds and regulates both mTORC1 and mTORC2, controlling their localization and cell growth.
| Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key r... | Genetic/biochemical (Rac1) | Rac1 / mTORC1 / mTORC2 | Mammalian cells | Rac1 is a critical regulator of both mTORC1 and mTORC2, controlling cell size | null | null | null | null | https://mtor-atlas.org/study/SAC2011/ |
WOL2015 | Sestrin2 is a leucine sensor for the mTORC1 pathway | Wolfson RL; Sabatini DM et al. | 2,015 | Science | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1126/science.aab2674 | 26,449,471 | PMC4698017 | Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1.
| Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including... | Biochemical/genetic (Sestrin2) | Sestrin2 / GATOR2 / Rag / mTORC1 | Mammalian cells | Sestrin2 is a leucine sensor for mTORC1; leucine (not arginine) binding relieves Sestrin2 inhibition | null | null | null | null | https://mtor-atlas.org/study/WOL2015/ |
OKA2013 | Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma | Okazaki H; Matsunaga N; Fujioka T; Okazaki F; Akagawa Y; Tsurudome Y; Ono M; Kuwano M; Koyanagi S; Ohdo S | 2,013 | Cancer Research | C - Animal | 4 - Animal Study | Animal | RenCa tumour-bearing mice; NIH 3T3 cells | Yes | 10.1158/0008-5472.CAN-12-3241 | 24,253,377 | null | In mouse kidney tumours, active phosphorylated mTOR and total mTOR protein followed a 24-hour rhythm, set by the clock through the ubiquitin ligase Fbxw7. Giving everolimus when mTOR was high improved survival compared with other dosing times. Same drug, same dose - the clock time of dosing changed the outcome.
| Circadian clock systems regulate many biologic functions, including cell division and hormone secretion in mammals. In this study, we explored the effects of circadian control on the pivot cell growth regulatory mTOR, the activity of which is deregulated in tumor cells compared with normal cells. Specifically, we inves... | Everolimus dosed at different times of day | mTOR; Fbxw7; DBP | Mouse | Dosing everolimus at the mTOR peak improved survival of tumour-bearing mice | null | null | null | null | https://mtor-atlas.org/study/OKA2013/ |
BO2026 | Molecular and metabolic dysregulation of lung cancer in developing anti-tumor activity by gambogic acid mediated mTOR signaling: in vitro and computational study. | Bo S, Liao Y, Chen X, Liu C, Pang J | 2,026 | 3 Biotech | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human lung cancer cell lines | Yes | 10.1007/s13205-026-04938-1 | 42,459,409 | PMC13369087 | Gambogic acid exerts anti-tumor activity in lung cancer cells by targeting and inhibiting mTOR signaling, supported by computational docking and in vitro experiments in cell lines; no in vivo or human data.
| Gambogic acid (GA), a natural xanthonoid compound, was investigated for its anticancer activity in lung cancer via mTOR signaling inhibition using computational and in vitro approaches. GA demonstrated high lipophilicity and docking interactions with mTOR pathway components, resulting in anti-proliferative and pro-apop... | Gambogic acid | mTOR signaling pathway | Human (cell line) | Inhibition of mTOR signaling; anti-proliferative and pro-apoptotic effects in lung cancer cells | null | null | null | null | https://mtor-atlas.org/study/BO2026/ |
YIN2026 | Substrate recognition and transport mechanism of the human proton-coupled amino-acid transporter 1 (SLC36A1) | Yin J; Yang M et al. | 2,026 | Nature Communications | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Recombinant human protein (cryo-EM) | Yes | 10.1038/s41467-026-75306-z | 42,414,312 | null | Cryo-EM structures of human PAT1 (SLC36A1) in apo and substrate-bound states reveal a convergent binding mode for diverse zwitterionic amino acids. This is a structural study; PAT1's role in lysosomal amino acid export and mTORC1 activation comes from earlier work.
| The proton-coupled amino-acid transporter SLC36A1 (hPAT1) is an atypical H+-driven carrier and mediates the intestinal absorption of a wide array of zwitterionic amino-acid analogs, including many compounds with central nervous-system (CNS) activity, as well as the activation of the mTORC1 pathway and the export of ami... | Structural/biochemical (cryo-EM of SLC36A1/PAT1, apo + 3 substrate-bound states) | SLC36A1 (PAT1) / lysosomal amino acid efflux / mTORC1 activation | Human (recombinant protein, cryo-EM; no animal/cell phenotype data) | Reveals the structural basis for the substrate promiscuity of PAT1; its role in lysosomal amino acid export and mTORC1 activation is prior work | null | null | null | null | https://mtor-atlas.org/study/YIN2026/ |
MIAO2026 | Chronic Kidney Disease Risk Posed by 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) Benzene (EDPrB): An AOP of mTOR-Mediated Autophagy Dysregulation. | Miao C; Zhang B; Yu W; Li Y; Cao Z | 2,026 | Environmental science & technology | C - Animal | 4 - Animal Study | Mechanism | Mouse (Kunming) + HK-2 human cell line | Yes | 10.1021/acs.est.6c06697 | null | null | In mice, the environmental pollutant EDPrB accumulates in the kidney and causes CKD via mTOR hyperactivation, leading to autophagy dysregulation, inflammation and fibrosis; rapamycin rescue identified mTOR as the molecular initiating event, with corroborating data in HK-2 human kidney cells.
| 1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB), a highly polluting fluorinated liquid-crystal monomer (FLCM), accumulates in the kidneys over the long term. Exposure to EDPrB can induce inflammatory responses and fibrosis in human renal cortical proximal tubule epithelial cells (HK-2), posing a risk... | EDPrB (fluorinated liquid crystal monomer) / Rapamycin | mTOR-autophagy | Mouse + Human cell line | In mice and HK-2 cells, mTOR hyperactivation causes autophagy dysregulation leading to CKD | null | null | null | null | https://mtor-atlas.org/study/MIAO2026/ |
JEW2015 | Metabolism. Differential regulation of mTORC1 by leucine and glutamine | Jewell JL; Guan KL et al. | 2,015 | Science | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1126/science.1259472 | 25,567,907 | PMC4384888 | Glutamine activates mTORC1 via a Rag-independent, Arf1-dependent route distinct from leucine.
| The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuo... | Biochemical/genetic | mTORC1 / Rag GTPases | Mammalian cells | Leucine activates mTORC1 via the Rags; glutamine activates it Rag-independently – differential regulation | null | null | null | null | https://mtor-atlas.org/study/JEW2015/ |
BCH2026 | Rapamycin-induced fatty liver in mice is attenuated by chloroquine co-treatment in an ERRα-dependent manner | B'chir W; Giguère V et al. | 2,026 | Journal of Endocrinology | C - Animal | 4 - Animal Study | Side effect | Mouse (rapamycin-induced MASLD model; ERRα-null mice) | Yes | 10.1530/JOE-26-0176 | 42,544,714 | null | Chloroquine co-treatment attenuates rapamycin-induced hepatic steatosis (a known mTORC1-inhibitor side effect) in mice, and this rescue depends on the nuclear receptor ERRα; RNA-seq shows chloroquine reverses rapamycin-driven upregulation of lipid-metabolism genes, with ERRα identified as a top transcriptional regulato... | Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), remains a major health concern world-wide. Hepatic steatosis manifests by the aberrant accumulation of lipids in hepatocytes. We have previously shown that pharmacological inhibition of mTOR ... | Chloroquine co-treatment with rapamycin | ERRα (Esrra) / mTORC1 | Mouse | Chloroquine co-treatment attenuates rapamycin-induced hepatic steatosis in an ERRα-dependent manner | null | null | null | null | https://mtor-atlas.org/study/BCH2026/ |
ZHO2001 | Role of AMP-activated protein kinase in mechanism of metformin action | Zhou G et al. | 2,001 | J Clin Invest | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Rat; hepatocytes; skeletal muscle | Yes | 10.1172/JCI13505 | 11,602,624 | PMC209533 | Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis.
| Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AM... | Metformin | AMPK (→ ACC; indirect mTORC1) | Rat; hepatocytes; skeletal muscle | Metformin activates AMPK, explaining its glucose- and lipid-lowering effects | null | null | null | null | https://mtor-atlas.org/study/ZHO2001/ |
SZW2021 | Regulation and metabolic functions of mTORC1 and mTORC2 | Szwed A; Jacinto E et al. | 2,021 | Physiological reviews | D - Mechanistic/Review | Narrative Review | Review | Review | Yes | 10.1152/physrev.00026.2020 | 33,599,151 | PMC8424549 | Comprehensive review of the regulation and metabolic functions of mTORC1 and mTORC2.
| Cells metabolize nutrients for biosynthetic and bioenergetic needs to fuel growth and proliferation. The uptake of nutrients from the environment and their intracellular metabolism is a highly controlled process that involves cross talk between growth signaling and metabolic pathways. Despite constant fluctuations in n... | Not applicable (review) | mTORC1 / mTORC2 | Review | Reviews how mTORC1/2 integrate growth signaling with metabolism | null | null | null | null | https://mtor-atlas.org/study/SZW2021/ |
ARR2015 | Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system | Arriola Apelo SI; Lamming DW et al. | 2,015 | Aging cell | C - Animal | 4 - Animal Study | Animal | Mouse | Yes | 10.1111/acel.12405 | 26,463,117 | PMC4717280 | Intermittent rapamycin regimens (weekly, or every 5 days) largely spared glucose tolerance, pyruvate tolerance, fasting glucose and insulin, beta-cell function and the immune system, while still inhibiting mTORC1 -- unlike daily dosing, which impaired all of them. IMPORTANT SCOPE: this study measured side effects only.... | Inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA-approved drug rapamycin has been shown to promote lifespan and delay age-related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and im... | Rapamycin – alternative/intermittent dosing regimens | mTORC1 (vs mTORC2) | Mouse | Intermittent regimens and rapalogs inhibit mTORC1 while largely sparing glucose tolerance and immune function; no survival endpoint was measured | 2 mg/kg rapamycin administered daily (1x/day), weekly (1x/7 days), once every three days (1x/3 days), or once every five days (1x/5 days) to 9-week-old male C57BL/6J mice for 2-8 weeks. | 9-11 male C57BL/6J mice per treatment group for glucose tolerance tests; 3-6 mice per group for blood rapamycin concentration; 4-9 mice per group for insulin/HOMA2 measurements; 6 mice per treatment for islet analysis. | Daily rapamycin treatment significantly impaired glucose tolerance (20–116% increase in blood glucose, 71% increase in AUC), while weekly (1x/7 days) or 1x/5 days rapamycin treatment did not impair glucose tolerance. Rapamycin 1x/3 days significantly impaired glucose tolerance. Daily rapamycin inhibited both mTORC1 (S6... | No lifespan or healthspan endpoint. Side-effect endpoints only; benefit retention is inferred, not tested. | https://mtor-atlas.org/study/ARR2015/ |
GOU2023 | The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease | Goul C; Zoncu R et al. | 2,023 | Nature reviews. Molecular cell biology | D - Mechanistic/Review | Narrative Review | Review | Review | Yes | 10.1038/s41580-023-00641-8 | 37,612,414 | null | Authoritative review of the molecular basis of nutrient sensing and signalling by mTORC1 in disease.
| The Ser/Thr kinase mechanistic target of rapamycin (mTOR) is a central regulator of cellular metabolism. As part of mTOR complex 1 (mTORC1), mTOR integrates signals such as the levels of nutrients, growth factors, energy sources and oxygen, and triggers responses that either boost anabolism or suppress catabolism. mTOR... | Not applicable (review) | mTORC1 nutrient-sensing machinery | Review | Reviews the molecular basis of nutrient sensing by mTORC1 and its role in metabolism and disease | null | null | null | null | https://mtor-atlas.org/study/GOU2023/ |
EFE2012 | Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival | Efeyan A; Sabatini DM et al. | 2,012 | Nature | C - Animal | 4 - Animal Study | Animal | Mouse (RagA GTP knock-in) | Yes | 10.1038/nature11745 | 23,263,183 | PMC4000705 | Rag-GTPase control of mTORC1 is essential for neonatal autophagy and survival to fasting.
| The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates organismal growth in response to many environmental cues, including nutrients and growth factors. Cell-based studies showed that mTORC1 senses amino acids through the RagA-D family of GTPases (also known as RRAGA, B, C and D), but their importance... | Genetic – constitutively active RagA(GTP) knock-in | mTORC1 / Rag GTPases | Mouse (RagA GTP knock-in) | Constitutive RagA→mTORC1 blocks fasting-induced autophagy in neonates → death on postnatal day 1 when fasted | not stated | not stated | Treatment of pups at birth with rapamycin significantly delayed the death of fasted RagA GTP/GTP neonates from ~14 h to ~21 h (p<0.01). | not stated | https://mtor-atlas.org/study/EFE2012/ |
HAR2004 | The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins | Harrington LS; Findlay GM; Lamb RF et al. | 2,004 | The Journal of Cell Biology | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells (TSC1/TSC2-null MEFs, human cells) | Yes | 10.1083/jcb.200403069 | 15,249,583 | null | One half of the discovery of mTORC1's main negative feedback loop. When mTORC1/S6K1 activity is left switched on, S6K1 phosphorylates IRS-1 and represses its expression, so the insulin receptor can no longer signal to PI3K. This is the textbook explanation for why blocking mTORC1 paradoxically raises Akt activity, and ... | Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is req... | Genetic loss of TSC1/TSC2; S6K1 activity manipulation | S6K1 -> IRS-1 -> PI3K/Akt | Mammalian cells | Sustained S6K1 activity depletes IRS-1 and uncouples the insulin receptor from PI3K | null | null | null | null | https://mtor-atlas.org/study/HAR2004/ |
MAN2014 | mTOR inhibition improves immune function in the elderly | Mannick JB et al. | 2,014 | Science Translational Medicine | B - Human | 2 - Human Clinical Trial | Human | Humans, RCT, older adults | Yes | 10.1126/scitranslmed.3009892 | 25,540,326 | null | Low-dose everolimus improved influenza vaccine response by ~20% and reduced PD-1 expression on T lymphocytes.
| Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span in all species studied to date, and in mice delays the onset of age-related diseases and comorbidities. However, it is unknown if mTOR inhibition affects aging or its consequences in humans. To begin to assess the effects of mTOR inhibitio... | Everolimus (RAD001), low dose | mTORC1 | Human – elderly adults, RCT | Improved influenza vaccine response (~20%) and reduced PD-1 expression on T cells | null | null | null | null | https://mtor-atlas.org/study/MAN2014/ |
HUA2013 | mTORC2 controls actin polymerization required for consolidation of long-term memory | Huang W; Zhu PJ; Zhang S; Zhou H; Stoica L; Galiano M; Krnjevic K; Roman G; Costa-Mattioli M | 2,013 | Nature Neuroscience | C - Animal | 4 - Animal Study | Mechanism | Conditional Rictor-knockout mice (postnatal forebrain) and Drosophila | null | 10.1038/nn.3351 | 23,455,608 | PMC3615448 | Conditional deletion of Rictor in the postnatal mouse forebrain reduced mTORC2 activity and selectively impaired long-term memory and the late phase of hippocampal LTP, with a comparable long-term-memory deficit in dTORC2-deficient flies. Hippocampal actin polymerisation was reduced, and restoring it rescued both L-LTP... | A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which cont... | Conditional postnatal forebrain Rictor deletion; dTORC2-deficient flies; actin-polymerisation rescue; mTORC2-activating compound | mTORC2 / Rictor; actin polymerisation | Mouse; Drosophila | Rictor deletion impairs long-term memory and late-phase LTP; restoring actin polymerisation rescues both | null | null | null | null | https://mtor-atlas.org/study/HUA2013/ |
GUR2017 | mTORC2 Promotes Tumorigenesis via Lipid Synthesis | Guri Y; Hall MN et al. | 2,017 | Cancer cell | C - Animal | 4 - Animal Study | Animal | Mouse; cells | Yes | 10.1016/j.ccell.2017.11.011 | 29,232,555 | null | mTORC2 promotes tumorigenesis through control of de novo lipid synthesis.
| Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC... | Genetic mTOR-driven mouse model | mTORC2 | Mouse; cells | Hepatic mTORC2 promotes de novo fatty-acid/lipid synthesis (sphingolipids, glycerophospholipids) driving steatosis → hepatocellular carcinoma | null | null | null | null | https://mtor-atlas.org/study/GUR2017/ |
CHU1992 | Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases | Chung J; Blenis J et al. | 1,992 | Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | T cells; in vitro | Yes | 10.1016/0092-8674(92)90643-q | 1,377,606 | null | Rapamycin-FKBP12 complex blocks growth-factor activation of p70 S6 kinase, linking the drug to a specific mitogenic pathway.
| The macrolide rapamycin blocks cell cycle progression in yeast and various animal cells by an unknown mechanism. We demonstrate that rapamycin blocks the phosphorylation and activation of the 70 kd S6 protein kinases (pp70S6K) in a variety of animal cells. The structurally related drug FK506 had no effect on pp70S6K ac... | Rapamycin (± FK506) | FKBP / p70 S6 kinase | T cells; in vitro | Rapamycin blocks activation of the p70 S6 kinases; FK506 reverses it (FKBP-dependent) | null | null | null | null | https://mtor-atlas.org/study/CHU1992/ |
SCI2014 | Mammalian target of rapamycin signaling in cardiac physiology and disease | Sciarretta S; Sadoshima J et al. | 2,014 | Circulation research | D - Mechanistic/Review | Narrative Review | Review | Review | Yes | 10.1161/CIRCRESAHA.114.302022 | 24,481,845 | PMC3995130 | Review of mTOR signalling in cardiac physiology and disease.
| The protein kinase mammalian or mechanistic target of rapamycin (mTOR) is an atypical serine/threonine kinase that exerts its main cellular functions by interacting with specific adaptor proteins to form 2 different multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 regulates protein sy... | Not applicable (review) | mTORC1 / mTORC2 | Review | Reviews mTOR roles in cardiac physiology and disease | null | null | null | null | https://mtor-atlas.org/study/SCI2014/ |
WANG2026 | Amino acid homeostasis by CORVET/HOPS: A metabolic and stress resilience checkpoint for T cells | Wang J; Ni Z; Zhang Xinxin; He L; Cheng X; Huang L; Ye H; Li P; Zhao TJ; Du X | 2,026 | Proceedings of the National Academy of Sciences | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mouse T cells (conditional VPS18 / VPS11 knockout, in vitro and in vivo) | Yes | 10.1073/pnas.2601318123 | 42,647,134 | null | Identifies the CORVET and HOPS endolysosomal tethering complexes as upstream suppliers of intracellular amino acids in activated T cells, acquired via macropinocytosis. Loss of the core subunits VPS18 or VPS11 starves the cell of amino acids, switches on the integrated stress response and shuts down mTORC1; enforced mT... | Amino acid sufficiency is critical for T cell metabolic reprogramming, yet how T cells maintain amino acid homeostasis remains poorly defined. Here, we identify the CORVET and HOPS (CORVET/HOPS) tethering complexes as essential upstream regulators. In activated T cells, they sustain intracellular amino acid levels by p... | Genetic ablation of CORVET/HOPS subunits VPS18 or VPS11; BIM deletion; enforced mTORC1 activity | CORVET/HOPS tethering complexes; mTORC1; integrated stress response | Mouse (T cells, in vitro and in vivo) | CORVET/HOPS loss causes amino acid scarcity, ISR activation and mTORC1 failure, abrogating T cell immunity | null | null | null | null | https://mtor-atlas.org/study/WANG2026/ |
XIE2026 | Glutamine alleviates bisphenol A-induced jejunal injury in piglets involving mitochondrial function restoration and AMPK-mTOR signaling regulation. | Xie J; Liu Z; Liu W et al. | 2,026 | Ecotoxicology and Environmental Safety | C - Animal | 4 - Animal Study | Animal | Piglet; porcine intestinal epithelial cells | Yes | 10.1016/j.ecoenv.2026.120698 | 42,660,031 | null | Glutamine supplementation alleviated bisphenol A-induced jejunal injury in piglets, restoring mitochondrial energy metabolism and barrier integrity alongside modulation of AMPK-mTOR signalling.
| Bisphenol A (BPA) disrupts intestinal homeostasis and promotes epithelial injury in piglets. Glutamine (Gln) is a vital energy substrate for intestinal epithelial cells. Piglet and porcine intestinal epithelial cell models were used. BPA exposure impaired intestinal morphology and barrier integrity, with reduced tight ... | Dietary glutamine supplementation | AMPK-mTOR; mitochondrial energy metabolism | Pig | Improved tight junction expression, epithelial renewal and mitochondrial function under BPA stress | null | null | null | null | https://mtor-atlas.org/study/XIE2026/ |
WALTER2026 | [Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial. | Walter T; Jann H; Ansquer C; Deshayes E; Garcia-Carbonero R; Teule A et al. | 2,026 | Lancet | B - Human | 2 - Human Clinical Trial | Human | Human RCT | Yes | 10.1016/S0140-6736(26)00604-5 | 42,392,118 | null | Phase 3 open-label RCT (n=309, 2:1): 177Lu-edotreotide gave longer PFS than everolimus (23.9 vs 14.1 months; HR 0.67) with fewer grade 3-4 treatment-related adverse events (18% vs 40%), supporting PRRT in early lines for progressive SSTR-positive GEP-NETs.
| Peptide receptor radionuclide and targeted therapy are both approved treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs), but clinical evidence for preferred sequencing is scarce. The COMPETE trial evaluated the efficacy and harms of peptide receptor radionuclide ther... | Everolimus (mTOR inhibitor) vs [177Lu]Lu-edotreotide | mTORC1 | Human | PRRT ([177Lu]Lu-edotreotide) gave longer PFS than everolimus, with fewer grade 3-4 treatment-related adverse events, in treatment-naive or pretreated SSTR-positive GEP-NETs | null | null | null | null | https://mtor-atlas.org/study/WALTER2026/ |
YAO2026 | Salvianolic Acid B Enhances Motor Function Recovery after Spinal Cord Injury in Association with AKT/mTOR/HIF-1α Pathway Activation and Angiogenesis. | Yao J; Chen Yingfeng; Pan F; Zhang S | 2,026 | Biological & Pharmaceutical Bulletin | C - Animal | 4 - Animal Study | Animal | Rat (spinal cord injury model) | Yes | 10.1248/bpb.b26-00280 | 42,649,073 | null | Salvianolic acid B improved motor recovery, neuronal survival and angiogenesis after rat spinal cord injury in association with AKT/mTOR/HIF-1α activation; the effects were reversed by the AKT inhibitor capivasertib.
| Spinal cord injury (SCI) is a devastating condition with limited treatment options. Salvianolic acid B (SalB), a natural compound from Salvia miltiorrhiza, shows therapeutic potential but its mechanisms in SCI remain unclear. This study combined network pharmacology, molecular docking and in vivo experiments using a ra... | Salvianolic acid B; capivasertib (AZD5363) as AKT inhibitor control | AKT/mTOR/HIF-1α; AKT1; angiogenesis | Rat | Improved motor function, reduced tissue damage, enhanced neuronal survival and angiogenesis; abolished by AKT inhibition | null | null | null | null | https://mtor-atlas.org/study/YAO2026/ |
CUI2026 | Forsythoside A Alleviates Hypertensive Nephropathy by Promoting Mitophagy and Inhibiting Ferroptosis via ASCL1-CCNB1/mTOR Pathway. | Cui X; Yang D; Zhang Z et al. | 2,026 | Journal of Ethnopharmacology | C - Animal | 4 - Animal Study | Animal | C57BL/6 mouse; NRK-52E rat kidney cells | Yes | 10.1016/j.jep.2026.122346 | 42,665,168 | null | Forsythoside A binds ASCL1 and blocks the downstream CCNB1/mTOR axis, promoting mitophagy and suppressing ferroptosis to protect against Ang II-induced hypertensive nephropathy in mice — without lowering blood pressure.
| Forsythoside A (FTA), the primary bioactive component of Forsythiae Fructus, exhibits anti-inflammatory and antioxidant activity. Hypertensive nephropathy (HN) models were established in C57BL/6 mice and NRK-52E cells using Ang II. FTA mitigated Ang II-induced renal injury by reducing renal dysfunction markers (Cr, BUN... | Forsythoside A | ASCL1-CCNB1/mTOR; mitophagy; ferroptosis | Mouse; rat kidney epithelial cells | Reduced renal dysfunction markers and inflammation; increased mitophagy, decreased ferroptosis | null | null | null | null | https://mtor-atlas.org/study/CUI2026/ |
BEN2008 | Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy | Bentzinger CF; Rueegg MA et al. | 2,008 | Cell metabolism | C - Animal | 4 - Animal Study | Animal | Mouse (muscle raptor/rictor KO) | Yes | 10.1016/j.cmet.2008.10.002 | 19,046,572 | null | In mice, muscle-specific raptor loss (not rictor) causes dystrophy, showing mTORC1 is essential for muscle homeostasis.
| Mammalian target of rapamycin (mTOR) is a central controller of cell growth. mTOR assembles into two distinct multiprotein complexes called mTOR complex 1 (mTORC1) and mTORC2. Here we show that the mTORC1 component raptor is critical for muscle function and prolonged survival. In contrast, muscles lacking the mTORC2 co... | Genetic – muscle-specific raptor KO (and rictor KO) | mTORC1 (raptor) vs mTORC2 (rictor) | Mouse (muscle raptor/rictor KO) | In mice, raptor loss (not rictor) causes progressive muscular dystrophy and metabolic changes – mTORC1 essential for muscle | null | null | null | null | https://mtor-atlas.org/study/BEN2008/ |
SAB1994 | RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs | Sabatini DM et al. | 1,994 | Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cell culture | Yes | 10.1016/0092-8674(94)90570-3 | 7,518,356 | null | Discovery of the protein RAFT1 (today's mTOR) as the direct target of the FKBP12-rapamycin complex; founding paper of the entire mTOR field.
| The immunosuppressants rapamycin and FK506 bind to the same intracellular protein, the immunophilin FKBP12. The FKB12-FK506 complex interacts with and inhibits the Ca(2+)-activated protein phosphatase calcineurin. The target of the FKBP12-rapamycin complex has not yet been identified. We report that a protein complex c... | Biochemical (FKBP12-rapamycin affinity purification) | RAFT1 (mTOR/FRAP) / FKBP12 | Mammalian cell culture | Identifies RAFT1 (mammalian TOR) as the FKBP12-rapamycin target, homologous to yeast TORs | null | null | null | null | https://mtor-atlas.org/study/SAB1994/ |
UMX2004 | Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity | Um SH; Thomas G et al. | 2,004 | Nature | C - Animal | 4 - Animal Study | Animal | Mouse (S6K1 KO) | Yes | 10.1038/nature02866 | 15,306,821 | null | S6K1 deletion protects mice from age- and diet-induced obesity and enhances insulin sensitivity.
| Elucidating the signalling mechanisms by which obesity leads to impaired insulin action is critical in the development of therapeutic strategies for the treatment of diabetes. Recently, mice deficient for S6 Kinase 1 (S6K1), an effector of the mammalian target of rapamycin (mTOR) that acts to integrate nutrient and ins... | Genetic – S6K1 knockout | S6K1 (downstream of mTORC1) | Mouse (S6K1 KO) | S6K1 loss protects against age- and diet-induced obesity and enhances insulin sensitivity | null | null | null | null | https://mtor-atlas.org/study/UMX2004/ |
SAR2006 | Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB | Sarbassov DD; Ali SM; Sengupta S; Sheen JH; Hsu PP; Bagley AF; Markhard AL; Sabatini DM | 2,006 | Molecular Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Multiple human/mouse cell lines | Yes | 10.1016/j.molcel.2006.03.029 | 16,603,397 | null | The molecular explanation for rapamycin's dark side. Short-term rapamycin only hits mTORC1, but LONG-term treatment also strips down mTORC2 in many cells, cutting Akt signaling. This is the mechanistic root of the insulin-resistance side effect later shown in mice (see Lamming 2012) - crucial for anyone dosing rapamyci... | The drug rapamycin has important uses in oncology, cardiology, and transplantation medicine, but its clinically relevant molecular effects are not understood. When bound to FKBP12, rapamycin interacts with and inhibits the kinase activity of a multiprotein complex composed of mTOR, mLST8, and raptor (mTORC1). The disti... | Rapamycin (prolonged treatment) | mTORC2 / Akt | Multiple human/mouse cell lines | Prolonged rapamycin inhibits mTORC2 assembly and Akt/PKB in some cells – mTORC2 is not always rapamycin-insensitive | null | null | null | null | https://mtor-atlas.org/study/SAR2006/ |
EVA2026 | PTEN regulates microtubule polymerization via mTORC2, but not mTORC1, in peripheral sensory neurons | Evans S; Reglewski J; Rose H; Lewis C; Nayak A; Minsky C; McNeil E; Knowles B; Wang W; Li M; Luikart BW; Hong J | 2,026 | eNeuro | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mouse peripheral sensory neuron cultures (Pten-KO with Raptor or Rictor co-deletion, both sexes) | Yes | 10.1523/ENEURO.0116-26.2026 | 42,642,329 | null | Uses Raptor (mTORC1) versus Rictor (mTORC2) co-deletion on a Pten-knockout background to ask which complex carries the growth signal to the microtubule cytoskeleton. Suppressing mTORC2 — but not mTORC1 — returns the accelerated microtubule polymerisation and neuronal hypertrophy of Pten-KO neurons to wild-type levels, ... | Peripheral neuropathy affects over 18 million adults in the U.S., but therapeutic outcomes are poor due to a lack of regenerative treatments. Pten is a strong negative regulator of cell growth, and Pten-KO drives axonal regeneration in various neuronal subtypes potentially via downstream regulation of stability of the ... | Genetic: Pten knockout with Raptor (mTORC1) or Rictor (mTORC2) co-deletion | mTORC2 (RICTOR); microtubule cytoskeleton; PTEN | Mouse (peripheral sensory neuron cultures) | mTORC2, not mTORC1, mediates PTEN-dependent microtubule polymerization and neuronal hypertrophy at the growth cone | null | null | null | null | https://mtor-atlas.org/study/EVA2026/ |
GUR2016 | mTOR Signaling Confers Resistance to Targeted Cancer Drugs | Guri Y; Hall MN et al. | 2,016 | Trends in cancer | D - Mechanistic/Review | Narrative Review | Review | Review | Yes | 10.1016/j.trecan.2016.10.006 | 28,741,507 | null | Review of how mTOR signalling confers resistance to targeted cancer therapies.
| Cancer is a complex disease and a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, the clinical benefits of such drugs are at best transient due to tumors displaying intrinsic or adaptive resistance. The un... | Not applicable (review) | mTOR | Review | mTOR signaling is a major compensatory pathway conferring resistance to targeted cancer drugs | null | null | null | null | https://mtor-atlas.org/study/GUR2016/ |
MOR2013 | mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation | Morita M; Sonenberg N et al. | 2,013 | Cell metabolism | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1016/j.cmet.2013.10.001 | 24,206,664 | null | mTORC1 controls mitochondrial biogenesis and activity through 4E-BP-dependent translation.
| mRNA translation is thought to be the most energy-consuming process in the cell. Translation and energy metabolism are dysregulated in a variety of diseases including cancer, diabetes, and heart disease. However, the mechanisms that coordinate translation and energy metabolism in mammals remain largely unknown. The mec... | Genetic/pharmacologic (mTORC1 / 4E-BP) | mTORC1 / 4E-BP | Mammalian cells | mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translation | null | null | null | null | https://mtor-atlas.org/study/MOR2013/ |
FEL2009 | Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2 | Feldman ME; Apsel B; Uotila A; Loewith R; Knight ZA; Ruggero D; Shokat KM | 2,009 | PLoS Biology | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mouse fibroblasts + primary cells | Yes | 10.1371/journal.pbio.1000038 | 19,209,957 | PMC2637922 | The parallel discovery to Thoreen 2009 (same year), from the Shokat lab. Their TORKinibs (PP242, PP30) block mTOR's active site, hitting both complexes and shutting down cap-dependent translation that rapamycin misses. Together these two papers established a whole new drug class beyond rapamycin.
| The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth fa... | ATP-competitive mTOR active-site inhibitors (vs rapamycin) | mTORC1 & mTORC2 | Mouse fibroblasts + primary cells | Active-site inhibitors block rapamycin-resistant outputs of mTORC1/2 (e.g. 4E-BP1), unlike rapamycin | null | null | null | null | https://mtor-atlas.org/study/FEL2009/ |
IYE2012 | Genome sequencing identifies a basis for everolimus sensitivity | Iyer G; Solit DB et al. | 2,012 | Science | B - Human | 3 - Human Observational | Human | Human (patient) + sequencing | Yes | 10.1126/science.1226344 | 22,923,433 | PMC3633467 | Genome sequencing of a single exceptional everolimus responder implicates TSC1 loss as the sensitivity basis. An n-of-1 observation, hypothesis-generating rather than confirmatory.
| Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among ... | Everolimus (mTOR inhibitor) | mTOR / TSC1 | Human – metastatic bladder cancer patient + tumor sequencing | Loss-of-function TSC1 mutation explains an exceptional everolimus response; TSC1 mutated in ~8% of bladder cancers | Everolimus (mTOR inhibitor) in a phase II trial; whole-genome/targeted tumor sequencing of an exceptional responder. | 1 exceptional responder + targeted sequencing of additional bladder tumors; 3 further TSC1-nonsense tumors identified (2 minor responders: 17% and 24% regression; 1 with 7%). | Loss-of-function TSC1 mutation underlies the exceptional everolimus response. TSC1-mutant tumors stayed on everolimus longer (7.7 vs 2.0 months, p=0.004) with improved time to recurrence (4.1 vs 1.8 months). | Inference from rare responders; basis of mTOR-inhibitor sensitivity beyond TSC1/2 loss still incompletely understood. | https://mtor-atlas.org/study/IYE2012/ |
HOL2005 | mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events | Holz MK; Blenis J et al. | 2,005 | Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1016/j.cell.2005.10.024 | 16,286,006 | null | mTOR and S6K1 dynamically assemble the translation preinitiation complex on eIF3.
| In response to nutrients, energy sufficiency, hormones, and mitogenic agents, S6K1 phosphorylates several targets linked to translation. However, the molecular mechanisms whereby S6K1 is activated, encounters substrate, and contributes to translation initiation are poorly understood. We show that mTOR and S6K1 maneuver... | Biochemical | mTOR / S6K1 / eIF3 | Mammalian cells | mTOR and S6K1 dynamically associate with eIF3 to control translation preinitiation via ordered phosphorylation | null | null | null | null | https://mtor-atlas.org/study/HOL2005/ |
EGA2010 | Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy | Egan DF; Shaw RJ et al. | 2,010 | Science | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1126/science.1196371 | 21,205,641 | PMC3030664 | AMPK directly phosphorylates ULK1 to connect energy sensing to autophagy/mitophagy, opposing mTOR.
| Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is req... | Genetic/biochemical (AMPK–ULK1) | AMPK / ULK1 / mTORC1 | Mammalian cells (+ C. elegans) | AMPK phosphorylates ULK1 to connect energy sensing to autophagy/mitophagy | null | null | null | null | https://mtor-atlas.org/study/EGA2010/ |
SRI2026 | Nutrient/TOR signaling controls adipose mitochondrial transcription factor A (TFAM) to regulate organismal growth in Drosophila | Sriskanthadevan-Pirahas S et al. | 2,026 | FEBS Lett | C - Animal | 4 - Animal Study | Animal | Drosophila (larvae, fat body) | Yes | 10.1002/1873-3468.70427 | 42,572,502 | null | In Drosophila larvae, nutrient/TOR signaling in the fat body (a key nutrient-sensing tissue) post-transcriptionally suppresses the mitochondrial transcription factor TFAM, and this TOR→TFAM axis in fat-body tissue controls whole-body developmental growth — a mechanistic link between nutrient sensing and interorgan grow... | Animals must adapt their growth to fluctuations in nutrient availability to ensure proper development. While nutrient-sensing tissues coordinate organismal growth through interorgan signaling, the metabolic changes within these tissues that mediate whole-body growth control remain poorly understood. Using Drosophila la... | Genetic manipulation of TOR signaling in the fat body (Drosophila) | TOR → TFAM (mitochondrial transcription factor A) | Drosophila melanogaster (larvae) | TOR suppresses TFAM protein levels in the fat body; this axis controls organismal developmental growth | null | null | null | null | https://mtor-atlas.org/study/SRI2026/ |
VER2026 | Testosterone propionate maintains autophagic flux and mitochondrial integrity via regulation of the LC3B/p62/Beclin-1/mTOR axis in induced liver fibrosis. | Verma S, Vaishnav S, Yadav M, Verma A, Washimkar K | 2,026 | Journal of Molecular Histology | C - Animal | 4 - Animal Study | Animal | Rat | Yes | 10.1007/s10735-026-10905-0 | 42,461,311 | null | Testosterone propionate protects against CCl4-induced liver fibrosis by maintaining mTOR-regulated autophagic flux via the LC3B/p62/Beclin-1 axis, preserving mitochondrial integrity; castration worsens fibrosis by impairing this pathway.
| In a CCl4-induced chronic liver injury rat model, testosterone propionate was found to preserve autophagic flux and mitochondrial function. Androgen deprivation worsened hepatic damage, while testosterone treatment maintained the LC3B/p62/Beclin-1/mTOR axis and protected mitochondrial quality control and reduced apopto... | Testosterone propionate | mTOR / LC3B / p62 / Beclin-1 autophagy axis | Rat | Testosterone maintains mTOR-regulated autophagy and mitochondrial integrity; androgen deprivation impairs autophagy and worsens liver fibrosis | null | null | null | null | https://mtor-atlas.org/study/VER2026/ |
LIU2015 | PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex | Liu P; Wei W et al. | 2,015 | Cancer discovery | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1158/2159-8290.CD-15-0460 | 26,293,922 | PMC4631654 | PIP3 relieves SIN1 PH-domain autoinhibition to activate the mTORC2 kinase complex.
| mTOR serves as a central regulator of cell growth and metabolism by forming two distinct complexes, mTORC1 and mTORC2. Although mechanisms of mTORC1 activation by growth factors and amino acids have been extensively studied, the upstream regulatory mechanisms leading to mTORC2 activation remain largely elusive. Here, w... | Biochemical/genetic (SIN1 PH domain) | mTORC2 / SIN1 / PtdIns(3,4,5)P3 | Mammalian cells | PIP3 binds the SIN1 PH domain to relieve suppression of mTOR → activates mTORC2 | null | null | null | null | https://mtor-atlas.org/study/LIU2015/ |
LIST2026 | Growth Hormone Receptor Antagonism Extends Lifespan | List EO; Berryman DE; Lach GS; Minto DF; Weese K; Kopchick JJ | 2,026 | Aging cell | C - Animal | 4 - Animal Study | Animal | GHA transgenic mice expressing the bovine GH G119K receptor antagonist (line maintained since 1991), both sexes; independent 2-year-old frailty cohort | Yes | 10.1111/acel.70697 | 42,701,998 | null | Transgenic expression of a growth hormone receptor antagonist — the G119K mutant chemistry behind the FDA-approved drug Pegvisomant — significantly extended both median and maximal lifespan in male (p = 0.044; p = 0.0037) and female mice, with maximal lifespan extended by 186 and 265 days respectively. Two-year-old ant... | Interventions that disrupt growth hormone (GH) action are recognized as some of the most potent methods for extending lifespan. Accordingly, GH receptor antagonists (GHA) represent potential therapeutics to improve healthspan. Somavert (Pegvisomant for injection), used for treating patients with acromegaly, is currentl... | Transgenic growth hormone receptor antagonist (bovine GH G119K), lifelong expression | Growth hormone receptor (GHR) / GH-IGF-1 axis upstream of PI3K-Akt-mTOR | Mouse (GHA transgenic, both sexes) | Extended median and maximal lifespan in both sexes; reduced frailty and greater grip strength at 2 years despite increased adiposity | null | null | null | null | https://mtor-atlas.org/study/LIST2026/ |
MAN2021 | Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials | Mannick JB; Teo G; Bernardo P; Quinn D; Russell K; Klickstein L; Marshall W; Shergill S | 2,021 | Lancet Healthy Longevity | B - Human | 2 - Human Clinical Trial | Negative_result | Humans, phase 2b + phase 3 RCT (n=1024 phase 3) | Yes | 10.1016/S2666-7568(21)00062-3 | 33,977,284 | PMC8102040 | The crucial reality check. After the promising phase 2a, the large phase 3 trial (n=1024) FAILED its primary endpoint - RTB101 did not reduce clinically symptomatic respiratory illness (26% vs 25%, p=0.65). It still reliably switched on antiviral genes, so the biomarker moved but the clinical outcome did not. A textboo... | The COVID-19 pandemic highlights the need for therapies that improve immune function in older adults, including interferon (IFN)-induced antiviral immunity that declines with age. In a previous phase 2a trial, RTB101 (previously known as BEZ235), an oral mechanistic target of rapamycin (mTOR) inhibitor, was observed to... | RTB101 (BEZ235), oral mTOR inhibitor; ± everolimus | mTOR (TORC1/2) | Human – phase 2b + phase 3 RCT (n=1024) | Phase 3 FAILED its primary endpoint (no reduction in symptomatic respiratory infections, 26 vs 25%); antiviral genes still upregulated | RTB101 5 or 10 mg once daily (+/- everolimus in phase 2b); phase 3 used RTB101 10 mg once daily; oral, placebo-controlled. | Phase 2b + phase 3 across >1500 adults aged >=65 (phase 3 n=1024). | Phase 3 primary endpoint (proportion with >=1 clinically symptomatic respiratory illness) NOT met; RTB101 still upregulated IFN-induced antiviral gene expression. Biomarker moved, clinical outcome did not. | FDA changed the primary endpoint between phase 2b and phase 3 (symptom-based vs lab-confirmed), complicating comparison; positive biomarker did not translate to clinical benefit. | https://mtor-atlas.org/study/MAN2021/ |
JOS2024 | mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction | Joshi JN; Valvezan AJ et al. | 2,024 | Cell Reports | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human and mouse cell lines (synchronised populations; fixed-cell single-cell imaging) | Yes | 10.1016/j.celrep.2024.114543 | 39,067,023 | PMC12730006 | mTORC1 activity oscillates across the cell cycle (lowest in mitosis/G1, highest in S/G2) via the TSC complex, independent of Akt/Mek-Erk; low mTORC1 in G1 sensitizes cells to autophagy induction from the same partial inhibition or nutrient drop -- direct evidence that the TIMING/pattern of mTORC1 activity, not just its... | Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that is active in nearly all proliferating eukaryotic cells; however, it is unclear whether mTORC1 activity changes throughout the cell cycle. We find that mTORC1 activity oscillates from lowest in mitosis/G1 to highest in S/G2. The inte... | Partial mTORC1 inhibition; nutrient reduction; cell-cycle synchronization | mTORC1 / TSC complex | Human & mouse cell lines | mTORC1 activity oscillates across the cell cycle (low mitosis/G1, high S/G2); low-mTORC1 G1 cells are more sensitive to autophagy induction | null | null | null | null | https://mtor-atlas.org/study/JOS2024/ |
AWARE2026 | Rapamycin increases cerebral blood flow and modulates metabolic, inflammatory, and microbiome profiles in healthy middle-aged APOE4 carriers: a pilot single-arm trial. | Aware C; Neher CM; Woods C; Khegai O; Dwivedi AK; et al.; Lin AL | 2,026 | Journal of Cerebral Blood Flow and Metabolism | B - Human | 2 - Human Clinical Trial | Human | Human pilot single-arm trial, healthy middle-aged APOE4 carriers vs non-carriers | Yes | 10.1177/0271678X261490342 | 42,723,264 | null | Single-arm pilot trial: 1 mg/day rapamycin for 4 weeks in 23 cognitively normal adults aged 45 to 65. Cerebral blood flow rose by more than 15% across several brain regions in the nine APOE4 carriers, while non-carriers showed no significant change; metabolic and inflammatory profiles improved and the gut microbiome wa... | Carriers of the apolipoprotein E4 (APOE4) allele often develop cerebrovascular dysfunction and broader systemic alterations decades before the onset of Alzheimer's disease (AD) pathology or clinical symptoms. Early interventions that can improve these functions may help delay or slow AD progression. In this study, we r... | null | null | null | null | null | null | null | null | https://mtor-atlas.org/study/AWARE2026/ |
SAN2008 | The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 | Sancak Y; Sabatini DM et al. | 2,008 | Science | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Human cell lines | Yes | 10.1126/science.1157535 | 18,497,260 | PMC2475333 | Identifies the Rag GTPase family as the missing link that lets mTORC1 sense amino acids by controlling whether mTOR is positioned near its activator Rheb.
| The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. We find that the Rag proteins--a family of four related small guanosine triphosphatases (GTPases)--interact with mTORC1 i... | Genetic/biochemical (Rag GTPases) | Rag GTPases / raptor / mTORC1 | Human cell lines | Rag GTPases interact with raptor in an amino-acid-sensitive way and are necessary for amino-acid activation of mTORC1 | null | null | null | null | https://mtor-atlas.org/study/SAN2008/ |
ORE2006 | mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt | O'Reilly KE; Rosen N et al. | 2,006 | Cancer research | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Cancer cells | Yes | 10.1158/0008-5472.CAN-05-2925 | 16,452,206 | PMC3193604 | mTORC1 inhibition relieves feedback and activates upstream RTK-PI3K-Akt signalling.
| Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In ... | mTOR inhibition (rapamycin) | mTOR / IRS-1 / Akt / RTK | Cancer cells | mTOR inhibition relieves feedback and induces upstream RTK signaling → activates Akt (a resistance mechanism) | null | null | null | null | https://mtor-atlas.org/study/ORE2006/ |
LAW2019 | Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex | Lawrence RE; Zoncu R et al. | 2,019 | Science | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Structure; cells | Yes | 10.1126/science.aax0364 | 31,672,913 | PMC6945816 | Structure reveals the FLCN complex as a Rag-GTPase activation checkpoint gating mTORC1.
| The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes f... | Structural/biochemical (FLCN complex) | FLCN–FNIP2 / RagC / mTORC1 | Structure; cells | The lysosomal folliculin complex acts as a GAP for RagC, a checkpoint in nutrient-dependent mTORC1 activation | null | null | null | null | https://mtor-atlas.org/study/LAW2019/ |
VEL2026 | Anticipatory metabolic regulation drives the distinct and improved metabolic state of caloric restriction compared to Fasting-Refeeding cycles. | Velingkaar N; Astafev AA; Prabahar A; Maravillas MA; Trokhimenko E; Rom JB; Asi GJ; Piontkivska H; Jiang P; Kondratov RV | 2,026 | Cell Reports | C - Animal | 4 - Animal Study | Animal | Mouse | Yes | 10.1016/j.celrep.2026.118022 | 42,752,091 | null | Comparing caloric restriction (CR, one meal/day) to a fasting-refeeding-fasting (FRF) regimen with matched food intake and fasting duration, CR engages anticipatory, circadian-clock-aligned metabolic control (hepatic mTOR signaling, ketogenesis, metabolic gene coordination), whereas FRF responses track direct nutrient/... | Interest in fasting-based diets to improve metabolic health is growing. Caloric restriction (CR) with one meal per day includes an extended fasting component that contributes to its metabolic and longevity benefits, yet the role of fasting within CR remains unclear. Here, we compare CR with a fasting-refeeding-fasting ... | null | null | null | null | null | null | null | null | https://mtor-atlas.org/study/VEL2026/ |
YAN2026B | Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK | Yang Y; et al.; Yang X | 2,026 | Signal Transduction and Targeted Therapy | C - Animal | 4 - Animal Study | Animal | Aged mice (12-month-old) and Hepassocin(Fgl1)-knockout mice, partial-hepatectomy liver regeneration model; correlative human liver tissue (aged vs young) | Yes | 10.1038/s41392-026-02773-7 | 42,736,285 | null | Hepassocin (HPS/FGL1), a hepatokine, activates AMPK via an ANXA2-ERK-p90RSK-LKB1 cascade, restraining mTOR activity. Aged HPS-knockout mice show reduced LKB1/AMPK activation and elevated mTOR activity, impaired autophagy, exacerbated cellular senescence, and severely compromised liver regeneration after partial hepatec... | Liver aging significantly impairs hepatic function and regenerative capacity, increasing the risk of morbidity and mortality from chronic liver diseases. Identifying molecular regulators of these processes may reveal promising therapeutic targets. Although Hepassocin (HPS), a hepatokine with known hepatoprotective func... | Hepassocin (HPS/FGL1) genetic knockout; exogenous HPS administration; AMPK agonist AICAR | AMPK (via ANXA2-ERK-p90RSK-LKB1 axis); mTOR activity | Mouse (aged, 12-month, HPS-knockout); human liver tissue (correlative) | HPS activates AMPK/LKB1 and restrains mTOR; aged HPS-KO mice show elevated mTOR activity, impaired autophagy, exacerbated senescence and failed liver regeneration; AICAR or exogenous HPS rescues the phenotype | null | null | null | null | https://mtor-atlas.org/study/YAN2026B/ |
BAR2012 | Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1 | Bar-Peled L; Sabatini DM et al. | 2,012 | Cell | D - Mechanistic/Review | 5 - Mechanistic / In Vitro | Mechanism | Mammalian cells | Yes | 10.1016/j.cell.2012.07.032 | 22,980,980 | PMC3517996 | Ragulator is the guanine-nucleotide exchange factor activating the Rag GTPases on the lysosome.
| The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form ... | Biochemical/genetic (Ragulator) | Ragulator / Rag GTPases / mTORC1 | Mammalian cells | Ragulator is a GEF for RagA/B, activating the Rags to signal amino-acid levels to mTORC1 at the lysosome | null | null | null | null | https://mtor-atlas.org/study/BAR2012/ |
SOL2014 | The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice | Solon-Biet SM et al. | 2,014 | Cell Metabolism | C - Animal | 4 - Animal Study | Animal | Mouse, 25 ad libitum diets | Yes | 10.1016/j.cmet.2014.02.009 | 24,606,899 | PMC5087279 | Lifespan and cardiometabolic health were determined not by caloric intake but by the protein:carbohydrate ratio; a low protein ratio was associated with lower hepatic mTOR activation.
| The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intak... | Dietary – 25 diets varying protein:carb:fat, ad libitum | Nutrient/mTOR signaling (dietary protein) | Mouse (25 ad libitum diets) | Macronutrient ratio (low protein, high carb), not calorie intake, optimizes cardiometabolic health and longevity | 25 ad libitum diets differing in protein (5%–60%), fat (16%–75%), carbohydrate (16%–75%), and energy (8, 13, or 17 kJ/g of food) fed over a lifetime | 858 mice across 25 diets | Median lifespan increased by approximately 30% (from 95 to 125 weeks) as the protein-to-carbohydrate ratio decreased; not influenced by total calorie intake | not stated | https://mtor-atlas.org/study/SOL2014/ |
MOT2008 | Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial | Motzer RJ et al. | 2,008 | Lancet | B - Human | 2 - Human Clinical Trial | Human | Humans, phase III RCT (RECORD-1) | Yes | 10.1016/S0140-6736(08)61039-9 | 18,653,228 | null | Everolimus extended median progression-free survival from 1.9 to 4.0 months versus placebo in metastatic renal cell carcinoma.
| Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. We did a phase III, randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progresse... | Everolimus (RAD001) | mTORC1 | Human – phase III RCT (RECORD-1), metastatic renal cell carcinoma | Everolimus improved progression-free survival vs placebo after VEGF-targeted therapy failure | null | null | null | null | https://mtor-atlas.org/study/MOT2008/ |
End of preview. Expand in Data Studio
Oliver's mTOR Atlas
The mTOR pathway, mapped by what the evidence can actually carry. This dataset is the curated corpus behind mtor-atlas.org: 414 hand-selected studies on mTOR (mechanistic target of rapamycin) signalling, each labelled by the kind of study behind it, and a list of 149 pathway entities (genes and proteins, complexes, drugs, interventions, biological processes, diseases, outcomes, organelles, nutrients and conditions) that the studies refer to.
- Homepage: https://mtor-atlas.org
- Curator: Oliver Barton (ORCID 0009-0008-2025-2148)
- License: CC BY 4.0
- Dataset DOI (Zenodo, all versions): 10.5281/zenodo.22059963
- Companion paper (Figshare): "Ten percent human: an evidence-graded audit of the mTOR literature and the pathway's translational gap", 10.6084/m9.figshare.33772297
- Also registered with: bio.tools, FAIRsharing, Wikidata Q141256074
Files
studies.csv/studies.json: one row per study. Atlas ID (sid), title, authors, year, journal, study type (tier,pyramid), category and model system, DOI/PMID/PMCID, a one-line curated finding, the PubMed abstract and, where extracted, AI-assisted fields (intervention, target, species, effect, dose, sample size, effect size, limitations).atlas_urllinks to the record page.entities.csv/entities.json: one row per entity. Name, type, a technical and a plain-language description, synonyms, the number of linked studies and, for entities with their own page,atlas_url.
How the study-type labels work
The website shows five codes: S (synthesis of human data), H (human study), A (animal model), M (molecular or in vitro work) and R (narrative review). They say what kind of evidence a study is. They are not a quality ranking, and a careful animal study is not "worse" than a weak human one.
The tier column keeps the original stored letters, so read it through this mapping:
stored tier |
shown on the site |
|---|---|
A - Systematic review |
S |
B - Human |
H |
C - Animal |
A |
D - Mechanistic/Review |
M, or R when pyramid is Narrative Review |
A few rows carry Preprint or Registered trial instead.
Intended uses
- Evaluating biomedical QA or summarisation models on a small corpus where every row traces back to a DOI or PMID.
- Testing study-type classifiers against human curation.
- Knowledge-graph work on the mTOR pathway, with the entities file as a node list.
Limitations
This is a curated selection, not a systematic review of the whole mTOR field, so a paper's absence says nothing against it. The label describes study design, not effect size or statistical power. The corpus grows as new studies are added, and this Hub copy may lag the live site. For a fixed, citable snapshot use the Zenodo DOI. Current exports are always at https://mtor-atlas.org/data/.
Citation
@misc{olivers_mtor_atlas,
author = {Barton, Oliver},
title = {Oliver's mTOR Atlas},
year = {2026},
publisher = {Zenodo},
doi = {10.5281/zenodo.22059963},
url = {https://doi.org/10.5281/zenodo.22059963}
}
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