MTOR mechanistic target of rapamycin kinase
ENSG00000198793 · protein coding · Open Targets profile
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1- pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23426360, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29424687, ECO:0000269|PubMed:29567957, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31695197, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:35926713, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:36691768, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37751742}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.2188899964094162 (upper bound 0.26704999804496765). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 56 registry trials, updated in the last three years, of the most advanced drugs against MTOR (perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, CC-115, samotolisib, OSI-027, vistusertib, sapanisertib, voxtalisib, apitolisib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- John L HaysECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Nadene ZackCelcuity Inc · 2 of 2 trials Phase 2+
- Anwaar SaeedUPMC Hillman Cancer Center LAO · 1 of 1 trials Phase 2+
- Aref Al-KaliMayo Clinic Cancer Center LAO · 1 of 1 trials Phase 2+
- Birgit GeoergerGustave Roussy, Cancer Campus, Grand Paris · 1 of 1 trials Phase 2+
- Bradley McGregorDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
- David Y ReardonDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
- Donald W ParsonsChildren's Oncology Group · 1 of 1 trials Phase 2+
- Fabrice ANDREGustave Roussy, Villejuif · 1 of 1 trials Phase 2+
- Fabrice BARLESICHU Hopital Nord Marseille · 1 of 1 trials Phase 2+
- Gary W MiddletonUniversity of Birmingham · 1 of 1 trials Phase 2+
- Jacques VargaftigInstitut Curie - Hôpital René Huguenin · 1 of 1 trials Phase 2+
- John HeymachM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Jonathan KrellImperial College London · 1 of 1 trials Phase 2+
- Joseph W KimYale University Cancer Center LAO · 1 of 1 trials Phase 2+
Registry trials of perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, CC-115, samotolisib, OSI-027, vistusertib, sapanisertib, voxtalisib, apitolisib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 40 of 55 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
55 trials of drugs against MTOR were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, CC-115, samotolisib, OSI-027, vistusertib, sapanisertib, voxtalisib, apitolisib, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 55.
- suspended · 2026-10-09 · Medinol Ltd. · matched by the registry's drug synonyms“Study was not initiated in any site. Sponsor decided not to start the study”
- suspended · 2026-02-13 · Dana-Farber Cancer Institute · Gedatolisib“Funding and drug supply to continue the study are pending.”
- terminated · 2025-09-08 · Institut Curie · matched by the registry's drug synonyms“No objective response was observed at the first step. The treatment was considered ineffective, with a complete clinical trial suspension.”
- terminated · 2025-04-24 · Faeth Therapeutics · sapanisertib“Sponsor decision - funding issues”
- terminated · 2024-04-04 · National Cancer Institute (NCI) · Sapanisertib“Other - Lapse in funding”
- terminated · 2023-10-17 · National Cancer Institute (NCI) · Vistusertib“Drug supply issues”
- terminated · 2023-02-08 · Calithera Biosciences, Inc · matched by the registry's drug synonyms“More favorable safety profile was observed in QD schedule, therefore further enrollment in QW schedule was terminated.”
- terminated · 2022-10-14 · Fox Chase Cancer Center · matched by the registry's drug synonyms“Closed to accrual due to Funding Sponsor withdrawing support due to low accrual”
- withdrawn · 2022-09-30 · Luke, Jason, MD · NLG802 (indoximod Prodrug)“Lack of funding support.”
- terminated · 2022-09-27 · NewLink Genetics Corporation · Indoximod“Sponsor termination, not related to efficacy, safety or feasibility.”
- terminated · 2022-08-23 · National Cancer Institute (NCI) · Sapanisertib“Interim monitoring”
- terminated · 2022-07-26 · Kathy Miller · matched by the registry's drug synonyms“Funder Decision”
- withdrawn · 2022-05-27 · M.D. Anderson Cancer Center · Sapanisertib“No participants Enrolled”
- terminated · 2022-04-06 · NewLink Genetics Corporation · Indoximod“Lack of enrollment and changing landscape of standard of care.”
- terminated · 2021-02-16 · Angela Taber MD · Ridaforolimus“Determination to stop enrollment made due to funding”
- terminated · 2021-02-10 · Restorbio Inc. · matched by the registry's drug synonyms“Insufficient accrual rate”
- terminated · 2021-01-06 · Acerta Pharma BV · vistusertib“Sponsor's decision not to pursue further development of the combination in DLBCL”
- terminated · 2020-12-08 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Study did not meet Phase Ib primary objective to establish the maximum tolerated dose/recommended dose for Phase II”
- withdrawn · 2020-11-20 · SWOG Cancer Research Network · Sapanisertib“The pharmaceutical company sold the compound and pulled out.”
- terminated · 2020-05-28 · NewLink Genetics Corporation · matched by the registry's drug synonyms“Lack of enrollment.”
- withdrawn · 2020-04-28 · Abramson Cancer Center at Penn Medicine · Gedatolisib“due to business decision regarding the study drug.”
- terminated · 2020-03-12 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“Poor Accrual”
- withdrawn · 2020-03-12 · Gary Schwartz · matched by the registry's drug synonyms“The study was withdrawn, because no participants were enrolled in two years.”
- withdrawn · 2019-11-22 · Restorbio Inc. · Dactolisib“Phase 3 trial RTB-101-204 study did not meet its primary endpoint”
- terminated · 2019-10-04 · University of Florida · Gedatolisib“Slow accrual”
Paediatric incentives and obligations for MTOR's drugs
For perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, CC-115, samotolisib, OSI-027, vistusertib, sapanisertib, voxtalisib, apitolisib: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · MTOR is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, cc-115, samotolisib, osi-027, vistusertib, sapanisertib, voxtalisib, apitolisibRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, cc-115, samotolisib, osi-027, vistusertib, sapanisertib, voxtalisib, apitolisibRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, cc-115, samotolisib, osi-027, vistusertib, sapanisertib, voxtalisib, apitolisibRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, cc-115, samotolisib, osi-027, vistusertib, sapanisertib, voxtalisib, apitolisibRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 22 interventional studies of perhexiline, ridaforolimus, gedatolisib, dactolisib, indoximod, cc-115, samotolisib, osi-027, vistusertib, sapanisertib, voxtalisib, apitolisib include patients under 18; 5 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 26 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.