MTOR

Summary

MTOR (mechanistic target of rapamycin kinase, HGNC:3942) is a protein-coding gene on chromosome 1p36.22, encoding Serine/threonine-protein kinase mTOR (P42345). 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. In precision oncology, MTOR Mutation OR PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation OR AKT2 Mutation confers sensitivity to Sapanisertib in Solid Tumor (CIViC Level B); 16 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 98.3% of cancer cell lines).

The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene.

Source: NCBI Gene 2475 — RefSeq curated summary.

At a glance

• Gene–disease (curated): overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 3,062 total — 23 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 103
• Druggable target: yes — 164 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 17 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 11 cancer types
• Cancer dependency (DepMap): dependent in 98.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_004958

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3942
Approved symbol	MTOR
Name	mechanistic target of rapamycin kinase
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	mTOR, RAFT1, RAPT1, FLJ44809
Ensembl gene	ENSG00000198793
Ensembl biotype	protein_coding
OMIM	601231
Entrez	2475

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 11 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000361445, ENST00000376838, ENST00000455339, ENST00000473471, ENST00000476768, ENST00000490931, ENST00000495435, ENST00000703118, ENST00000703131, ENST00000703132, ENST00000703139, ENST00000703140, ENST00000703141, ENST00000703142, ENST00000703143, ENST00000703144, ENST00000875524, ENST00000875525, ENST00000934310, ENST00000934311, ENST00000934312, ENST00000934313, ENST00000934314, ENST00000934315

RefSeq mRNA: 3 — MANE Select: NM_004958 NM_001386500, NM_001386501, NM_004958

CCDS: CCDS127

Canonical transcript exons

ENST00000361445 — 58 exons

Exon	Start	End
ENSE00000743767	11199258	11199403
ENSE00000743769	11199541	11199703
ENSE00000743771	11204561	11204703
ENSE00000743775	11210814	11210906
ENSE00000743777	11212312	11212474
ENSE00000743779	11212796	11212908
ENSE00000743781	11213399	11213566
ENSE00000743783	11216148	11216234
ENSE00000743785	11228668	11228918
ENSE00000743788	11230925	11231054
ENSE00000743790	11231300	11231434
ENSE00000743792	11232436	11232528
ENSE00000743799	11237843	11238048
ENSE00000743801	11238402	11238617
ENSE00000743803	11240303	11240547
ENSE00000743805	11241553	11241681
ENSE00000743807	11243114	11243300
ENSE00000743810	11247625	11247733
ENSE00001041990	11129738	11129838
ENSE00001167814	11121979	11122126
ENSE00001167821	11124498	11124633
ENSE00001167829	11126622	11126796
ENSE00001167837	11127010	11127144
ENSE00001167844	11127624	11127806
ENSE00001167852	11128004	11128126
ENSE00001167858	11128454	11128552
ENSE00001167869	11128855	11128951
ENSE00001167905	11133080	11133197
ENSE00001167940	11144648	11144755
ENSE00001167950	11144968	11145045
ENSE00001167960	11146676	11146791
ENSE00001167966	11150126	11150226
ENSE00001167973	11157152	11157291
ENSE00001167981	11167442	11167517
ENSE00001435329	11209312	11209458
ENSE00001471842	11262445	11262551
ENSE00003482987	11139533	11139658
ENSE00003513153	11134351	11134466
ENSE00003571700	11139304	11139435
ENSE00003988093	11247819	11248094
ENSE00003988095	11114813	11114887
ENSE00003988097	11259248	11259423
ENSE00003988098	11106535	11107500
ENSE00003988104	11109290	11109370
ENSE00003988106	11112852	11112917
ENSE00003988108	11258485	11258593
ENSE00003988109	11109649	11109729
ENSE00003988111	11121246	11121368
ENSE00003988118	11108181	11108286
ENSE00003988125	11115396	11115468
ENSE00003988127	11114318	11114453
ENSE00003988131	11256933	11257165
ENSE00003988140	11117004	11117086
ENSE00003988141	11130529	11130777
ENSE00003988142	11255992	11256192
ENSE00003988147	11253839	11253973
ENSE00004023457	11234143	11234265
ENSE00004023458	11233398	11233487

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 93.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2083 / max 70.8203, expressed in 1787 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10292	7.9633	1766
10291	2.2450	1245

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.71	gold quality
cerebellar hemisphere	UBERON:0002245	92.28	gold quality
cerebellar cortex	UBERON:0002129	92.12	gold quality
left testis	UBERON:0004533	92.08	gold quality
right testis	UBERON:0004534	91.90	gold quality
gastrocnemius	UBERON:0001388	91.56	gold quality
right frontal lobe	UBERON:0002810	91.20	gold quality
muscle of leg	UBERON:0001383	91.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.73	gold quality
ventricular zone	UBERON:0003053	90.60	gold quality
apex of heart	UBERON:0002098	90.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.11	gold quality
testis	UBERON:0000473	90.10	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.04	gold quality
lower esophagus	UBERON:0013473	90.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.74	gold quality
tibial nerve	UBERON:0001323	89.65	gold quality
adenohypophysis	UBERON:0002196	89.59	gold quality
cerebellum	UBERON:0002037	89.47	gold quality
metanephros cortex	UBERON:0010533	89.43	gold quality
stromal cell of endometrium	CL:0002255	89.38	gold quality
right lobe of liver	UBERON:0001114	89.08	gold quality
cortical plate	UBERON:0005343	89.07	gold quality
right adrenal gland cortex	UBERON:0035827	88.85	gold quality
right adrenal gland	UBERON:0001233	88.58	gold quality
popliteal artery	UBERON:0002250	88.48	gold quality
tibial artery	UBERON:0007610	88.47	gold quality
right atrium auricular region	UBERON:0006631	88.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.96

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
FLCN	Activation
PIH1D1	Activation

Upstream regulators (CollecTRI, top): ATF4, CEBPB, PDX1, SOX2, SPI1

miRNA regulators (miRDB)

91 targeting MTOR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and mTOR itself is an ATP sensor. (PMID:11691993)
• phosphatic acid mediated mitogen activation of mTOR signaling (PMID:11729323)
• Atrophy and hypertrophy of skeletal muscle are associated with decreases and increases in Ser(2448) phosphorylation, a site in the mammalian target of rapamycin (mTOR) phosphorylated by protein kinase B (PKB) in vitro. (PMID:11884412)
• Predominant nuclear localization in normal and malignant cells in culture. (PMID:12000755)
• Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E (PMID:12080086)
• Syncytia from cells expressing the HIV-1 Env gene fused with cells expressing CD4/CXCR4 undergo apoptosis after nuclear translocation of mTOR, mTOR-mediated p53 phosphorylation, p53-dependent Bax upregulation & mitochondrial death pathway activation. (PMID:12145207)
• mTOR interacts with Raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. (PMID:12150925)
• mTOR-catalyzed phosphorylation of 4EBP1 in vitro and mTOR action in vivo require the participation of mTOR binding protein, raptor. (PMID:12150926)
• These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR). (PMID:12172553)
• FRAP is a CLIP-170 kinase positively regulating the MT-binding behavior of CLIP-170 (PMID:12231510)
• Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin; These studies position mTOR as an upstream activator of HIF-1 function in cancer cells (PMID:12242281)
• hamartin and tuberin function together to inhibit mammalian target of rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) (PMID:12271141)
• mTOR substrate specificity is regulated by serine in the rapamycin binding domain (PMID:12370290)
• the AMPK and mTOR signalling pathways are possibly linked. (PMID:12558800)
• raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs. (PMID:12604610)
• mammalian target of rapamycin regulates STAT1-dependent gene transcription by lipopolysaccharide and interferon-gamma (PMID:12807916)
• mTOR is a critical target for survival signals generated by phospholipase D in breast cancer cells. (PMID:12813467)
• Rheb is a mediator of MTOR. (PMID:12820960)
• TOR-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1 (PMID:12912989)
• Identification of domains of FRAP/mTOR which may mediate its association with the endoplasmic reticulum and the Golgi apparatus. (PMID:14578359)
• This review describes recent progress in understanding the control of the mTOR signaling pathway and the role of mTOR-interacting proteins. (PMID:14668532)
• K-Ras-mediated transformation of intestinal epitelial cells involves activation of the PI3K/mTOR pathway. (PMID:14729629)
• Thr2446 as a novel nutrient-regulated phosphorylation site on mTOR (PMID:14970221)
• Activation of hexosamine pathway affects glucose-induced phosphorylation of IRS-1. Impairs coupling of IRS-1 and PI 3-kinase and activativates Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway. (PMID:15001544)
• A new form of mTOR elucidates the molecular mechanism underlying mTOR-dependent regulation of RNA synthesis (PMID:15004009)
• PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells. (PMID:15028555)
• an intact PI3K/mTOR pathway is necessary for the ability of IFNalpha to induce apoptosis, whereas activation of the Jak-STAT pathway alone appears to be insufficient for this specific IFNalpha-induced effect (PMID:15056668)
• mTOR does not have a role in B-Raf kinase activity regulation by tuberin and Rheb (PMID:15150271)
• mTOR regulates PP5, which activates apoptosis signal-regulating kinase 1 signaling (PMID:15218033)
• Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress. (PMID:15292274)
• ANG II activates rapamycin-sensitive mTOR signaling pathway in human coronary smooth muscle cells and involves activation of phosphatidylinositol 3-kinase, p70(S6k), and eukaryotic initiation factor-4E, leading to activation of protein synthesis. (PMID:15317677)
• The rapid activation of PI3K-Akt/PKB-mTOR-p70(S6K) cascade by T3 provides a new molecular mechanism for thyroid hormone action (PMID:15388791)
• Human cytomegalovirus induces mechanisms to maintain the integrity of the eIF4F complex even when mTOR signaling is inhibited. (PMID:15452223)
• PKC-eta targets the Akt and mTOR signaling pathways (PMID:15489897)
• stromal cell-mediated apoptotic protection in B-lineage ALL is mediated by PI3K/mTOR and MEK via a synergistic mechanism (PMID:15496972)
• mTOR may play a major role in IL-12-induced IFN-gamma production by activated T cells (PMID:15522880)
• the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose transport in 3T3-L1 and human adipocytes (PMID:15576463)
• identification of an alternative survival signal that is dependent on phospholipase D and mTOR and is active in a breast cancer cell line where the phosphatidylinositol-3-kinase survival pathway is not active (PMID:15580312)
• Review. TOR is a transducer of information from various sources, including growth factors, energy sensors, hypoxia sensors, & components regulating growth & division. Blocking TOR mimics amino acid & growth factor deprivation & has a cytostatic effect. (PMID:15584862)
• mTOR/S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver and muscle (PMID:15604215)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtor	ENSDARG00000053196
mus_musculus	Mtor	ENSMUSG00000028991
rattus_norvegicus	Mtor	ENSRNOG00000009615
drosophila_melanogaster	mTor	FBGN0021796

Paralogs (5): ATM (ENSG00000149311), SMG1 (ENSG00000157106), ATR (ENSG00000175054), TRRAP (ENSG00000196367), PRKDC (ENSG00000253729)

Protein

Protein identifiers

Serine/threonine-protein kinase mTOR — P42345 (reviewed: P42345)

Alternative names: FK506-binding protein 12-rapamycin complex-associated protein 1, FKBP12-rapamycin complex-associated protein, Mammalian target of rapamycin, Mechanistic target of rapamycin, Rapamycin and FKBP12 target 1, Rapamycin target protein 1, Tyrosine-protein kinase mTOR

All UniProt accessions (7): A0A8V8TQ52, A0A8V8TQM6, A0A8V8TQN3, A0A8V8TQP2, A0A8V8TR74, A0A8V8TRG9, P42345

UniProt curated annotations — full annotation on UniProt →

Function. 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. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). 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. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). 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. 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. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at ‘Ser-758’, disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions. Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. The mTORC1 complex is inhibited in response to starvation and amino acid depletion. 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. Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity. The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output. 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. In contrast to mTORC1, mTORC2 is nutrient-insensitive. 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. mTORC2 also regulates the phosphorylation of SGK1 at ‘Ser-422’. 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. The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1. 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. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks.

Subunit / interactions. Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR. The mTORC1 complex is a 1 Md obligate dimer of two stoichiometric heterotetramers with overall dimensions of 290 A x 210 A x 135 A. It has a rhomboid shape and a central cavity, the dimeric interfaces are formed by interlocking interactions between the two MTOR and the two RPTOR subunits. The MLST8 subunit forms distal foot-like protuberances, and contacts only one MTOR within the complex, while the small AKT1S1/PRAS40 localizes to the midsection of the central core, in close proximity to RPTOR. mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity by blocking MTOR substrate-recruitment site. Component of the mechanistic target of rapamycin complex 2 (mTORC2), consisting in two heterotretramers composed of MTOR, MLST8, RICTOR and MAPKAP1/SIN1. Interacts with PLPP7 and PML. Interacts with PRR5 and RICTOR; the interaction is direct within the mTORC2 complex and interaction with RICTOR is enhanced by deubiquitination of RICTOR by USP9X. mTORC1 and mTORC2 associate with DEPTOR, which regulates their activity. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation. Interacts with UBQLN1. Interacts with TTI1 and TELO2. Interacts with CLIP1; phosphorylates and regulates CLIP1. Interacts with NBN. Interacts with HTR6. Interacts with BRAT1. Interacts with MEAK7 (via C-terminal domain); the interaction increases upon nutrient stimulation. Interacts with TM4SF5; the interaction is positively regulated by arginine and is negatively regulated by leucine. Interacts with GPR137B. Interacts with NCKAP1L. Interacts with TPCN1 and TPCN2; the interaction is required for TPCN1 and TPCN2 sensitivity to ATP. Interacts with ATP6V1A and with CRYAB, forming a ternary complex. Interacts with SLC38A7; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation. Interacts with TSPAN8.

Subcellular location. Lysosome membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell membrane. Mitochondrion outer membrane. Cytoplasm. Nucleus. PML body. Microsome membrane. Cytoplasmic vesicle. Phagosome.

Tissue specificity. Expressed in numerous tissues, with highest levels in testis.

Post-translational modifications. Autophosphorylates when part of mTORC1 or mTORC2. Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation. Phosphorylated at Ser-2448 by RPS6KB1. Phosphorylation in the kinase domain modulates the interactions of MTOR with RPTOR and AKT1S1/PRAS40 and leads to increased intrinsic mTORC1 kinase activity. Phosphorylation at Ser-2159 by TBK1 in response to growth factors and pathogen recognition receptors promotes mTORC1 activity. Phosphorylation at Ser-2159 by TBK1 in response to EGF growth factor promotes mTORC2 activity, leading to AKT1 phosphorylation and activation. Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity. Ubiquitinated at Lys-2066 by the SCF(FBXO22) complex via ‘Lys-27’-linked ubiquitination prevents mTORC1 substrate recruitment.

Disease relevance. Smith-Kingsmore syndrome (SKS) [MIM:616638] An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features. The disease is caused by variants affecting the gene represented in this entry. Focal cortical dysplasia 2 (FCORD2) [MIM:607341] A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The mTORC1 complex is activated in response to nutrients, growth factors or amino acids: activation requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD. Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1. Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1. The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8. The kinase activity of MTOR is inhibited by DEPTOR and AKT1S1. The non-canonical mTORC1 complex is independent of the RHEB GTPase and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 but not other mTORC1 substrates: it is activated by FLCN, which activates Rag GTPases RagC/RRAGC and RagD/RRAGD. MTOR is the target of the immunosuppressive and anti-cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and specifically inhibits its kinase activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 associates and is directly activated by ribosomes. mTORC2 may also be regulated by RHEB but in an indirect manner through the PI3K signaling pathway.

Domain organisation. The kinase domain (PI3K/PI4K) is intrinsically active but has a highly restricted catalytic center. The FAT domain forms three discontinuous subdomains of alpha-helical TPR repeats plus a single subdomain of HEAT repeats. The four domains pack sequentially to form a C-shaped a-solenoid that clamps onto the kinase domain.

Similarity. Belongs to the PI3/PI4-kinase family.

RefSeq proteins (3): NP_001373429, NP_001373430, NP_004949* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR003151	PIK-rel_kinase_FAT	Domain
IPR003152	FATC_dom	Domain
IPR009076	FRB_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR014009	PIK_FAT	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR024585	mTOR_dom	Domain
IPR026683	TOR_cat	Domain
IPR036738	FRB_sf	Homologous_superfamily
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR050517	DDR_Repair_Kinase	Family
IPR057564	HEAT_ATR	Domain

Pfam: PF00454, PF02259, PF02260, PF08771, PF11865, PF23593

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (349 total): helix 141, repeat 48, strand 39, sequence variant 31, turn 25, binding site 17, sequence conflict 14, modified residue 12, mutagenesis site 9, region of interest 7, domain 3, chain 1, compositionally biased region 1, cross-link 1

Structure

Experimental structures (PDB)

70 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4DRI	X-RAY DIFFRACTION	1.45
9DBO	X-RAY DIFFRACTION	1.55
5GPG	X-RAY DIFFRACTION	1.67
5WBH	X-RAY DIFFRACTION	1.75
4DRJ	X-RAY DIFFRACTION	1.8
3FAP	X-RAY DIFFRACTION	1.85
8PPZ	X-RAY DIFFRACTION	1.85
8XI9	X-RAY DIFFRACTION	1.85
9DL0	X-RAY DIFFRACTION	2
1NSG	X-RAY DIFFRACTION	2.2
2FAP	X-RAY DIFFRACTION	2.2
6M4U	X-RAY DIFFRACTION	2.2
4DRH	X-RAY DIFFRACTION	2.3
1AUE	X-RAY DIFFRACTION	2.33
9T94	ELECTRON MICROSCOPY	2.6
9ZBK	ELECTRON MICROSCOPY	2.6
1FAP	X-RAY DIFFRACTION	2.7
4FAP	X-RAY DIFFRACTION	2.8
8ER6	X-RAY DIFFRACTION	2.81
8ERA	ELECTRON MICROSCOPY	2.86
9T93	ELECTRON MICROSCOPY	2.86
9NGT	X-RAY DIFFRACTION	2.95
6ZWO	ELECTRON MICROSCOPY	3
9T7J	ELECTRON MICROSCOPY	3
9TDT	ELECTRON MICROSCOPY	3
8ER7	X-RAY DIFFRACTION	3.07
5WBY	X-RAY DIFFRACTION	3.1
8RCN	ELECTRON MICROSCOPY	3.1
9T92	ELECTRON MICROSCOPY	3.1
6M4W	X-RAY DIFFRACTION	3.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42345-F1	78.57	0.11

Antibody-complex structures (SAbDab): 2 — 9DBO, 9DL0

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (17): 1662; 1702; 1749; 2165; 2167; 2185; 2187; 2190; 2225; 2238; 2239; 2240 …

Post-translational modifications (13): 1, 567, 1162, 1218, 1261, 2159, 2164, 2173, 2446, 2448, 2478, 2481, 2066

Mutagenesis-validated functional residues (9):

Position	Phenotype
2066	complete loss ubiquitination by the scf(fbxo22) complex.
2159	reduces mtorc1-associated s-2481 autophosphorylation; when associated with a-2164. reduced activity of the mtorc1 comple
2159	mimics phosphorylation; leading to stronger phosphorylation of rps6kb1; when associated with e-2164. increased activity
2164	reduces mtorc1-associated s-2481 autophosphorylation; when associated with a-2159.
2164	stronger phosphorylation of rps6kb1; when associated with d-2159.
2173	increased mtor kinase activity.
2340	barely detectable kinase activity.
2357	kinase-dead mutant, loss of interaction with tm4sf5 and loss of lysosome membrane localization; when associated with i-2
2364	kinase-dead mutant, loss of interaction with tm4sf5 and loss of lysosome membrane localization; when associated with e-2

Function

Pathways and Gene Ontology

Reactome pathways

41 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1632852	Macroautophagy
R-HSA-165159	MTOR signalling
R-HSA-166208	mTORC1-mediated signalling
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9920951	Dengue virus modulates apoptosis
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-212436	Generic Transcription Pathway
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-2262752	Cellular responses to stress
R-HSA-3371556	Cellular response to heat stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-388841	Regulation of T cell activation by CD28 family
R-HSA-389356	Co-stimulation by CD28
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers

MSigDB gene sets: 1040 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CIRCADIAN_RHYTHM, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION

GO Biological Process (115): regulation of cell growth (GO:0001558), T-helper 1 cell lineage commitment (GO:0002296), heart morphogenesis (GO:0003007), heart valve morphogenesis (GO:0003179), energy reserve metabolic process (GO:0006112), ‘de novo’ pyrimidine nucleobase biosynthetic process (GO:0006207), inflammatory response (GO:0006954), DNA damage response (GO:0006974), cytoskeleton organization (GO:0007010), germ cell development (GO:0007281), regulation of cell size (GO:0008361), cellular response to starvation (GO:0009267), response to heat (GO:0009408), response to virus (GO:0009615), post-embryonic development (GO:0009791), negative regulation of autophagy (GO:0010507), positive regulation of lamellipodium assembly (GO:0010592), positive regulation of epithelial to mesenchymal transition (GO:0010718), positive regulation of myotube differentiation (GO:0010831), macroautophagy (GO:0016236), regulation of macroautophagy (GO:0016241), negative regulation of macroautophagy (GO:0016242), neuronal action potential (GO:0019228), cell projection organization (GO:0030030), positive regulation of cell growth (GO:0030307), positive regulation of actin filament polymerization (GO:0030838), T cell costimulation (GO:0031295), regulation of myelination (GO:0031641), protein destabilization (GO:0031648), response to nutrient levels (GO:0031667), cellular response to nutrient levels (GO:0031669), cellular response to nutrient (GO:0031670), TOR signaling (GO:0031929), cellular response to insulin stimulus (GO:0032869), regulation of actin cytoskeleton organization (GO:0032956), calcineurin-NFAT signaling cascade (GO:0033173), cellular response to amino acid starvation (GO:0034198), multicellular organism growth (GO:0035264), TORC1 signaling (GO:0038202), TORC2 signaling (GO:0038203)

GO Molecular Function (20): inositol hexakisphosphate binding (GO:0000822), RNA polymerase III type 1 promoter sequence-specific DNA binding (GO:0001002), RNA polymerase III type 2 promoter sequence-specific DNA binding (GO:0001003), RNA polymerase III type 3 promoter sequence-specific DNA binding (GO:0001006), TFIIIC-class transcription factor complex binding (GO:0001156), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), identical protein binding (GO:0042802), ribosome binding (GO:0043022), transmembrane transporter binding (GO:0044325), phosphoprotein binding (GO:0051219), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), protein-containing complex binding (GO:0044877)

GO Cellular Component (23): Golgi membrane (GO:0000139), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), lysosome (GO:0005764), lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), PML body (GO:0016605), dendrite (GO:0030425), TORC1 complex (GO:0031931), TORC2 complex (GO:0031932), phagocytic vesicle (GO:0045335), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
MTOR signalling	2
Intracellular signaling by second messengers	1
Autophagy	1
Signal Transduction	1
Cellular response to heat stress	1
Co-stimulation by CD28	1
VEGFA-VEGFR2 Pathway	1
Transcriptional Regulation by TP53	1
PI3K/AKT Signaling in Cancer	1
Regulation of TP53 Expression and Degradation	1
PTEN Regulation	1
Cellular response to starvation	1
Response of endothelial cells to shear stress	1
Dengue Virus-Host Interactions	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
RNA polymerase III cis-regulatory region sequence-specific DNA binding	3
protein kinase activity	3
protein binding	3
intracellular membrane-bounded organelle	3
cytoplasm	3
cellular response to stress	2
autophagy	2
binding	2
endomembrane system	2
TOR complex	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
T-helper cell lineage commitment	1
T-helper 1 cell differentiation	1
heart development	1
animal organ morphogenesis	1
heart valve development	1
anatomical structure morphogenesis	1
energy derivation by oxidation of organic compounds	1
pyrimidine nucleobase biosynthetic process	1
defense response	1
organelle organization	1
developmental process involved in reproduction	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
regulation of cellular component size	1
cellular response to nutrient levels	1
response to starvation	1
response to stress	1
response to temperature stimulus	1
response to other organism	1
multicellular organism development	1
multicellular organismal process	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1

Protein interactions and networks

STRING

8056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTOR	RICTOR	Q6R327	999
MTOR	RPTOR	Q8N122	999
MTOR	MLST8	Q9BVC4	999
MTOR	MAPKAP1	Q9BPZ7	998
MTOR	FKBP1A	P20071	998
MTOR	RHEB	Q15382	997
MTOR	DEPTOR	Q8TB45	997
MTOR	PRR5	P85299	997
MTOR	AKT1S1	Q96B36	997
MTOR	RPS6KB1	P23443	978
MTOR	ULK1	O75385	972
MTOR	TSC2	P49815	962
MTOR	AKT1	P31749	955
MTOR	EIF4EBP1	Q13541	952
MTOR	RPS6	P08227	947

IntAct

467 interactions, top by confidence:

A	B	Type	Score
MTOR	RPTOR	psi-mi:“MI:0915”(physical association)	0.980
RPTOR	MTOR	psi-mi:“MI:0914”(association)	0.980
RPTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.980
MTOR	RPTOR	psi-mi:“MI:0914”(association)	0.980
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
RICTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.970
MTOR	RICTOR	psi-mi:“MI:0915”(physical association)	0.970

BioGRID (967): RICTOR (Affinity Capture-Western), RPTOR (Affinity Capture-Western), AKT1S1 (Affinity Capture-Western), MTOR (Affinity Capture-Western), MTOR (Affinity Capture-Western), PRR5L (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MTOR (Affinity Capture-Western), AKT1S1 (Biochemical Activity), PRR5L (Biochemical Activity), EIF4EBP1 (Biochemical Activity), MTOR (Biochemical Activity), MTOR (Affinity Capture-Western), ILK (Affinity Capture-Western), RICTOR (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4ITC5, A1L1F4, A4L9P7, E9Q8I9, F1MKX4, F1QFR9, F1R2X6, F8VPU6, O94915, P21359, P42345, P42346, P51593, P97526, Q04690, Q14997, Q29RF7, Q2HJG5, Q498H0, Q4KLU7, Q4QXM3, Q4VA53, Q5F3U9, Q5F3V3, Q5R6J0, Q5SSW2, Q5TBA9, Q5U241, Q5VYK3, Q6A026, Q6DDM4, Q6GP04, Q6NRP2, Q6P4S8, Q6PDI5, Q6TRW4, Q7PX35, Q7TMY8, Q7Z3U7, Q7Z6Z7

Diamond homologs: A4IID4, A4QPH2, A9X1A0, B0KWC1, B1MTG7, B2KI64, B3EX61, B4UT09, E9Q3L2, O02810, O02811, O08561, O08662, O14356, O70173, P0CP60, P0CP61, P37297, P39104, P42345, P42346, P42356, P54677, Q0DJS1, Q0WPX9, Q49GP3, Q59LR2, Q6CAD2, Q6GN16, Q86C65, Q8BKC8, Q8N8J0, Q8SQY7, Q95Q95, Q9C680, Q9FMJ0, Q9FR53, Q9JLN9, Q9SXA1, Q9UBF8

SIGNOR signaling

166 interactions.

A	Effect	B	Mechanism
MTOR	“down-regulates activity”	EIF4EBP1	phosphorylation
AKT2	up-regulates	MTOR
RPS6KB1	“down-regulates activity”	MTOR	phosphorylation
“phosphatidic acid”	up-regulates	MTOR	“chemical activation”
MTOR	down-regulates	EIF4EBP2	phosphorylation
MTOR	up-regulates	EIF4EBP3	phosphorylation
MTOR	“up-regulates activity”	AKT	phosphorylation
RHEB	“up-regulates activity”	MTOR	binding
RPS6K	“down-regulates activity”	MTOR	phosphorylation
MTOR	up-regulates	STAT3	phosphorylation
sirolimus	down-regulates	MTOR	“chemical inhibition”
MTOR	up-regulates	RPS6KB2	phosphorylation
MTOR	“down-regulates activity”	AKT1S1	phosphorylation
FKBP8	down-regulates	MTOR	binding
MTOR	down-regulates	MAF1	phosphorylation
“AP 23573”	down-regulates	MTOR	“chemical inhibition”
everolimus	down-regulates	MTOR	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mTORC1-mediated signalling	9	46.5×	7e-11
Dengue virus modulates apoptosis	5	38.8×	9e-06
Constitutive Signaling by AKT1 E17K in Cancer	7	32.2×	2e-07
VEGFR2 mediated vascular permeability	6	26.6×	8e-06
CD28 dependent PI3K/Akt signaling	6	25.7×	8e-06
MTOR signalling	8	23.1×	2e-07
Regulation of TP53 Degradation	7	22.3×	3e-06
HSF1-dependent transactivation	5	17.2×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
TOR signaling	5	32.2×	1e-04
cellular response to nutrient levels	8	31.5×	1e-07
positive regulation of mitotic cell cycle	5	19.7×	1e-03
cellular response to amino acid stimulus	5	12.9×	5e-03
positive regulation of cell growth	8	12.3×	1e-04
negative regulation of autophagy	5	10.9×	7e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	10.6×	3e-03
regulation of apoptotic process	8	5.6×	7e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

mTOR deregulation has been observed in many cancer types. As a part of the PI3K/Akt pathway, there is a broad interest in mTOR biology across cancer types. mTOR inhibition has been investigated for nearly a decade. Everolimus, temsirolimus and zotarolimus are three of the more commonly used mTOR inhibitors used in clinical treatment today, with modest success.

From intOGen — cancer-driver classification: activating (oncogene-like) across 11 cancer types — BLCA, BRCA, CCRCC, CHRCC, CLLSLL, COADREAD, HCC, LGGNOS, PANET, RCC, UCEC.

Clinical variants and AI predictions

ClinVar

3062 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	28
Uncertain significance	1035
Likely benign	1335
Benign	405

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1296989	NM_004958.4(MTOR):c.5930C>G (p.Thr1977Arg)	Pathogenic
1339561	NM_004958.4(MTOR):c.257del (p.Gly86fs)	Pathogenic
156702	NM_004958.4(MTOR):c.5930C>A (p.Thr1977Lys)	Pathogenic
156703	NM_004958.4(MTOR):c.6644C>T (p.Ser2215Phe)	Pathogenic
156709	NM_004958.4(MTOR):c.7255G>A (p.Glu2419Lys)	Pathogenic
190121	NM_004958.4(MTOR):c.4448G>T (p.Cys1483Phe)	Pathogenic
217823	NM_004958.4(MTOR):c.5395G>A (p.Glu1799Lys)	Pathogenic
224088	NM_004958.4(MTOR):c.4785G>A (p.Met1595Ile)	Pathogenic
242349	NM_004958.4(MTOR):c.6981G>A (p.Met2327Ile)	Pathogenic
2579952	NM_004958.4(MTOR):c.4184A>G (p.Lys1395Arg)	Pathogenic
2672094	NM_004958.4(MTOR):c.4376C>A (p.Ala1459Asp)	Pathogenic
374796	NM_004958.4(MTOR):c.4447T>C (p.Cys1483Arg)	Pathogenic
376129	NM_004958.4(MTOR):c.6644C>A (p.Ser2215Tyr)	Pathogenic
376130	NM_004958.4(MTOR):c.4379T>C (p.Leu1460Pro)	Pathogenic
376453	NM_004958.4(MTOR):c.4448G>A (p.Cys1483Tyr)	Pathogenic
3774491	NM_004958.4(MTOR):c.4348T>G (p.Tyr1450Asp)	Pathogenic
4056380	NM_004958.4(MTOR):c.7289G>C (p.Arg2430Thr)	Pathogenic
417723	NM_004958.4(MTOR):c.7280T>C (p.Leu2427Pro)	Pathogenic
417724	NM_004958.4(MTOR):c.7280T>A (p.Leu2427Gln)	Pathogenic
417727	NM_004958.4(MTOR):c.4366T>G (p.Trp1456Gly)	Pathogenic
520633	NM_004958.4(MTOR):c.7238G>T (p.Ser2413Ile)	Pathogenic
584432	NM_004958.4(MTOR):c.5930C>T (p.Thr1977Ile)	Pathogenic
981176	NM_004958.4(MTOR):c.7501A>T (p.Ile2501Phe)	Pathogenic
1065618	NM_004958.4(MTOR):c.6227G>A (p.Arg2076Gln)	Likely pathogenic
1296993	NM_004958.4(MTOR):c.4468T>C (p.Trp1490Arg)	Likely pathogenic
1296997	NM_004958.4(MTOR):c.5005G>T (p.Ala1669Ser)	Likely pathogenic
1310128	NM_004958.4(MTOR):c.5380G>A (p.Ala1794Thr)	Likely pathogenic
1315046	NM_004958.4(MTOR):c.7076G>A (p.Gly2359Glu)	Likely pathogenic
1320130	NM_004958.4(MTOR):c.5912C>T (p.Ala1971Val)	Likely pathogenic
1339560	NM_004958.4(MTOR):c.6457A>G (p.Ile2153Val)	Likely pathogenic

SpliceAI

8698 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11108177:TCACC:T	donor_loss	1.0000
1:11108179:A:AC	donor_gain	1.0000
1:11108179:A:C	donor_loss	1.0000
1:11108179:AC:A	donor_gain	1.0000
1:11108179:ACCAG:A	donor_gain	1.0000
1:11108180:C:CG	donor_gain	1.0000
1:11108180:CC:C	donor_gain	1.0000
1:11108180:CCA:C	donor_gain	1.0000
1:11108180:CCAG:C	donor_gain	1.0000
1:11108180:CCAGC:C	donor_gain	1.0000
1:11108282:CCGAC:C	acceptor_gain	1.0000
1:11108283:CGAC:C	acceptor_gain	1.0000
1:11108283:CGACC:C	acceptor_gain	1.0000
1:11108285:ACCTA:A	acceptor_loss	1.0000
1:11108286:CCTA:C	acceptor_loss	1.0000
1:11108287:C:A	acceptor_loss	1.0000
1:11108287:C:CC	acceptor_gain	1.0000
1:11108288:T:G	acceptor_loss	1.0000
1:11108291:C:CT	acceptor_gain	1.0000
1:11108293:C:CT	acceptor_gain	1.0000
1:11108294:A:T	acceptor_gain	1.0000
1:11109286:TCAC:T	donor_loss	1.0000
1:11109287:CAC:C	donor_loss	1.0000
1:11109288:A:AC	donor_gain	1.0000
1:11109288:A:C	donor_loss	1.0000
1:11109289:C:CC	donor_gain	1.0000
1:11109289:C:CT	donor_loss	1.0000
1:11109367:CCAA:C	acceptor_gain	1.0000
1:11109368:CAA:C	acceptor_gain	1.0000
1:11109368:CAAC:C	acceptor_gain	1.0000

AlphaMissense

16807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11107491:G:C	F2548L	1.000
1:11107491:G:T	F2548L	1.000
1:11107493:A:G	F2548L	1.000
1:11107500:C:A	W2545C	1.000
1:11107500:C:G	W2545C	1.000
1:11108182:A:G	W2545R	1.000
1:11108182:A:T	W2545R	1.000
1:11108198:G:C	C2539W	1.000
1:11108199:C:T	C2539Y	1.000
1:11108200:A:G	C2539R	1.000
1:11108202:A:G	L2538P	1.000
1:11108221:C:G	A2532P	1.000
1:11108232:A:G	L2528P	1.000
1:11109295:A:G	L2508P	1.000
1:11109295:A:T	L2508H	1.000
1:11109297:C:A	K2507N	1.000
1:11109297:C:G	K2507N	1.000
1:11109299:T:C	K2507E	1.000
1:11109307:A:T	V2504D	1.000
1:11109328:G:T	A2497D	1.000
1:11114331:C:A	W2429C	1.000
1:11114331:C:G	W2429C	1.000
1:11114333:A:G	W2429R	1.000
1:11114333:A:T	W2429R	1.000
1:11114347:T:A	D2424V	1.000
1:11114347:T:C	D2424G	1.000
1:11114348:C:G	D2424H	1.000
1:11114353:A:T	V2422D	1.000
1:11114355:A:C	F2421L	1.000
1:11114355:A:T	F2421L	1.000

dbSNP variants (sampled 300 via entrez): RS1000009921 (1:11141193 G>A,T), RS1000102236 (1:11161844 C>T), RS1000158996 (1:11203196 G>A), RS1000223398 (1:11245812 A>T), RS1000233522 (1:11257901 G>A), RS1000249530 (1:11227883 T>C), RS1000250655 (1:11156001 AT>A,ATT), RS1000260530 (1:11160194 A>G), RS1000264226 (1:11116281 G>A), RS1000311924 (1:11196749 A>T), RS1000321853 (1:11209415 T>C), RS1000347093 (1:11109968 C>A,G,T), RS1000357970 (1:11204143 C>T), RS1000376825 (1:11239629 GCA>G), RS1000411685 (1:11153853 G>A)

Disease associations

OMIM: gene MIM:601231 | disease phenotypes: MIM:616638, MIM:607341, MIM:607086, MIM:619681, MIM:618774, MIM:615513

GenCC curated gene-disease

Disease	Classification	Inheritance
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	Autosomal dominant
macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	AD

Mondo (12): macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MONDO:0014716), isolated focal cortical dysplasia type II (MONDO:0011818), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (MONDO:0100283), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215), CEBALID syndrome (MONDO:0032908), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), immunodeficiency 14 (MONDO:0014222), overgrowth syndrome (MONDO:0019716), hemimegalencephaly (MONDO:0020492)

Orphanet (12): Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (Orphanet:457485), Isolated focal cortical dysplasia type II (Orphanet:268994), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Facial dysmorphism-Intellectual disability-rhombencephalosynapsis syndrome (Orphanet:693549), Rare genetic intellectual disability (Orphanet:183757), Activated PI3K-delta syndrome (Orphanet:397596), Activated PI3K-delta syndrome 1 (Orphanet:693661), Overgrowth syndrome (Orphanet:93460), Hemimegalencephaly (Orphanet:99802), Hereditary papillary renal cell carcinoma (Orphanet:47044), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

103 total (30 of 103 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000154	Wide mouth
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000267	Cranial asymmetry
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000331	Short chin
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000648	Optic atrophy
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000929	Abnormal skull morphology
HP:0000957	Cafe-au-lait spot
HP:0001028	Hemangioma
HP:0001053	Hypopigmented skin patches
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001101_1	Corneal curvature	4.000000e-13
GCST002502_3	Corneal curvature	6.000000e-18
GCST002783_403	Body mass index	2.000000e-06
GCST002783_529	Body mass index	9.000000e-06
GCST003475_1	Beard thickness	4.000000e-07
GCST006288_594	Heel bone mineral density	1.000000e-10
GCST006288_701	Heel bone mineral density	2.000000e-06
GCST011329_1	Body mass index and type 2 diabetes (pairwise)	2.000000e-08
GCST90002392_148	Mean corpuscular volume	4.000000e-09
GCST90002396_110	Mean reticulocyte volume	5.000000e-16
GCST90002397_170	Mean spheric corpuscular volume	1.000000e-21
GCST90020024_1247	A body shape index	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D065705	Hemimegalencephaly	C05.660.207.536.500; C10.500.507.400.249.500; C16.131.621.207.532.500; C16.131.666.507.400.249.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C537067	Focal cortical dysplasia of Taylor (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2221341 (PROTEIN COMPLEX), CHEMBL2842 (SINGLE PROTEIN), CHEMBL4296661 (PROTEIN COMPLEX), CHEMBL4296662 (PROTEIN COMPLEX), CHEMBL4523674 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523999 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

164 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,000,707 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL117785	TETRABENAZINE	4	9,645
CHEMBL1201182	TEMSIROLIMUS	4	25,195
CHEMBL1276308	MIFEPRISTONE	4	30,535
CHEMBL1375743	ZIPRASIDONE HYDROCHLORIDE	4	7,696
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL142635	NAFTOPIDIL	4	3,611
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL1480	FELODIPINE	4	30,761
CHEMBL1484	NICARDIPINE	4	30,866
CHEMBL1489	AZACITIDINE	4	97,123
CHEMBL15023	TRIFLUPERIDOL	4	2,646
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL1626	CLEMASTINE	4	17,590
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL185	FLUOROURACIL	4	299,469
CHEMBL185073	PANCURONIUM	4	11
CHEMBL1908360	EVEROLIMUS	4
CHEMBL193	NIFEDIPINE	4
CHEMBL2	PRAZOSIN	4
CHEMBL21731	MAPROTILINE	4
CHEMBL219916	DOMPERIDONE	4
CHEMBL2396661	ALPELISIB	4
CHEMBL269732	TACROLIMUS ANHYDROUS	4
CHEMBL305660	EBASTINE	4
CHEMBL313972	MASOPROCOL	4
CHEMBL3218576	COPANLISIB	4

Clinical evidence (CIViC)

Drug × variant × indication: 17 predictive associations from 17 curated evidence items; also 2 functional, 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
MTOR Mutation OR PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation OR AKT2 Mutation	Sapanisertib	Solid Tumor	Sensitivity/Response	CIViC B	EID12075
MTOR E2014K AND MTOR E2419K	Pazopanib + Everolimus	Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID1438
MTOR Mutation	Everolimus + Pazopanib	Bladder Carcinoma	Sensitivity/Response	CIViC C	EID705
MTOR F2108L	Everolimus	Thyroid Gland Carcinoma	Resistance	CIViC C	EID1110
MTOR C1483Y	Sirolimus	T-cell Acute Lymphoblastic Leukemia	Sensitivity/Response	CIViC D	EID1320
MTOR E1799K	Sirolimus	Clear Cell Renal Cell Carcinoma	Sensitivity/Response	CIViC D	EID1321
MTOR E1799K	Everolimus	Megalencephaly	Sensitivity/Response	CIViC D	EID9486
MTOR E1799K	Everolimus	Focal Cortical Dysplasia	Sensitivity/Response	CIViC D	EID9489
MTOR H1968Y	PI3K/BET Inhibitor LY294002 + Capivasertib	Melanoma	Sensitivity/Response	CIViC D	EID713
MTOR P2213S	Capivasertib + PI3K/BET Inhibitor LY294002	Melanoma	Sensitivity/Response	CIViC D	EID722
MTOR S2215Y	Sirolimus	Endometrial Adenocarcinoma	Sensitivity/Response	CIViC D	EID1319
MTOR T1977K	Sirolimus	Solid Tumor	Sensitivity/Response	CIViC D	EID7323
MTOR A2034V	Sirolimus	Breast Cancer	Resistance	CIViC D	EID1547
MTOR A2034V	RapaLink-1 + MTOR Kinase Inhibitor AZD8055	Breast Cancer	Resistance	CIViC D	EID1548
MTOR F2108L	Sirolimus	Breast Cancer	Resistance	CIViC D	EID1543
MTOR M2327I	MTOR Kinase Inhibitor AZD8055	Breast Cancer	Resistance	CIViC D	EID1544
MTOR M2327I	RapaLink-1 + Sirolimus	Breast Cancer	Resistance	CIViC D	EID1545

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2024627	Efficacy	3	everolimus	Breast Neoplasms;Kidney Neoplasms;Neuroendocrine Tumors

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12139042	MTOR		0.00	0
rs2295080	MTOR		0.00	0
rs1057079	MTOR		0.00	0
rs2024627	MTOR	3	1.50	1	everolimus
rs2295079	MTOR		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — FRAP subfamily

Most potent curated ligand interactions (42 total), top 25:

Ligand	Action	Affinity	Parameter
ridaforolimus	Inhibition	9.7	pIC50
torin 1	Inhibition	9.54	pIC50
AZD8055	Inhibition	9.1	pIC50
sapanisertib	Inhibition	8.85	pKi
gedatolisib	Inhibition	8.8	pIC50
everolimus	Inhibition	8.7	pIC50
compound 82 [PMID: 21332118]	Inhibition	8.7	pKi
vistusertib	Inhibition	8.55	pIC50
torin 2	Inhibition	8.55	pIC50
panulisib	Inhibition	8.36	pIC50
WYE-354	Inhibition	8.3	pIC50
compound 7 [PMID: 31955578]	Inhibition	8.25	pIC50
dactolisib	Inhibition	8.22	pIC50
PP-242	Inhibition	8.1	pIC50
CZ415	Inhibition	8.07	pIC50
neolymphostin A	Inhibition	8.0	pKd
XL388	Inhibition	8.0	pIC50
PP121	Inhibition	8.0	pIC50
onatasertib	Inhibition	8.0	pIC50
KU-0063794	Inhibition	8.0	pIC50
PQR620	Inhibition	7.97	pKi
bimiralisib	Inhibition	7.92	pKd
compound 12b [PMID: 31465220]	Inhibition	7.85	pKd
eCF309	Inhibition	7.82	pIC50
PF-04691502	Inhibition	7.8	pKi

Binding affinities (BindingDB)

2745 measured of 3223 human assays (3226 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-[6-(dimethylamino)-3-pyridinyl]-1-[4-(2-hydroxyethoxy)cyclohexyl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.102 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-[(2R)-2-hydroxypropanoyl]piperidin-4-yl]-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.11 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.114 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(4-hydroxycyclohexyl)-8-(1H-indazol-5-yl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.145 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxybenzoic acid	IC50	0.15 nM	US-9102670: Pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors
1-[1-(2-methoxyacetyl)piperidin-4-yl]-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.167 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(1-acetylpiperidin-4-yl)-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.191 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(1-acetylpiperidin-4-yl)-8-(6-amino-3-pyridinyl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.252 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
US9102670, 1cg	IC50	0.26 nM	US-9102670: Pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors
8-[6-(dimethylamino)-3-pyridinyl]-1-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.264 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-(2-aminopyrimidin-5-yl)-1-(4-hydroxycyclohexyl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.273 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-[6-(dimethylamino)-3-pyridinyl]-1-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.281 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
3-methyl-1-(1-methylpiperidin-4-yl)-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.282 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-[6-(dimethylamino)-3-pyridinyl]-3-methyl-1-(oxan-4-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.298 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-aminoacetyl)piperidin-4-yl]-3-methyl-8-(6-methyl-3-pyridinyl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.32 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-hydroxyacetyl)piperidin-4-yl]-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.32 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
2-[4-[8-(6-methoxy-3-pyridinyl)-3-methyl-2-oxoimidazo[4,5-c][1,5]naphthyridin-1-yl]piperidin-1-yl]acetamide	KI	0.339 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(4-hydroxycyclohexyl)-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.366 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
N-[[4-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]phenyl]methyl]methanesulfonamide	IC50	0.39 nM	US-9102670: Pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors
1-(1-acetylpiperidin-4-yl)-8-[6-(dimethylamino)-3-pyridinyl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.391 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-[6-(dimethylamino)-3-pyridinyl]-1-[1-[(2R)-2-hydroxypropanoyl]piperidin-4-yl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.397 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[(2R)-1-hydroxypropan-2-yl]-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.438 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(1-acetylpiperidin-4-yl)-8-(6-methoxy-3-pyridinyl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.478 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-[6-(dimethylamino)-3-pyridinyl]-3-methyl-1-piperidin-4-ylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.5 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(4-hydroxycyclohexyl)-8-(6-methoxy-3-pyridinyl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.5 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[4-(2-hydroxyethoxy)cyclohexyl]-8-(6-methoxy-3-pyridinyl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.5 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-[6-(dimethylamino)-3-pyridinyl]-1-[1-(2-hydroxyacetyl)piperidin-4-yl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.505 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-7-fluoro-1-[(1R,3R)-3-methoxycyclopentyl]-3-methylimidazo[4,5-c]quinolin-2-one	IC50	0.507 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-(4-hydroxycyclohexyl)-8-(6-methoxy-3-pyridinyl)-3H-imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.51 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
(4S)-4-(3-chloro-4-fluorophenyl)-3-[3-[3-fluoro-4-(1H-1,2,4-triazol-5-yl)phenyl]pyrazolo[1,5-a]pyrimidin-5-yl]-1,3-oxazolidin-2-one	IC50	0.51 nM	US-8865726: Substituted pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors
(4S)-4-(5-fluoro-2-pyridinyl)-3-[3-[3-fluoro-4-(1H-1,2,4-triazol-5-yl)phenyl]pyrazolo[1,5-a]pyrimidin-5-yl]-1,3-oxazolidin-2-one	IC50	0.51 nM	US-8865726: Substituted pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors
(4S)-4-(4-fluorophenyl)-3-[3-[3-fluoro-4-(1H-1,2,4-triazol-5-yl)phenyl]pyrazolo[1,5-a]pyrimidin-5-yl]-1,3-oxazolidin-2-one	IC50	0.51 nM	US-8865726: Substituted pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors
1-(1-acetylpiperidin-4-yl)-8-(1H-indazol-4-yl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.513 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
8-(2-aminopyrimidin-5-yl)-3-methyl-1-(oxan-4-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.529 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-hydroxyacetyl)piperidin-4-yl]-3-methyl-8-(6-methyl-3-pyridinyl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.532 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
3-methyl-1-(1-propanoylpiperidin-4-yl)-8-quinolin-3-ylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.539 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-3-methyl-8-quinolin-3-ylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.568 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-hydroxyacetyl)piperidin-4-yl]-8-(1H-indazol-4-yl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.575 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(3-methoxycyclobutyl)-8-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]-3H-imidazo[4,5-c]quinolin-2-one	IC50	0.589 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-[4-(2-hydroxyethoxy)cyclohexyl]-8-(6-methoxy-3-pyridinyl)-3H-imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.644 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
[4-[3-[2-(6-amino-3-pyridinyl)ethynyl]-2-methyl-4-pyridinyl]-2-chlorophenyl]-(4-cyclopropylpiperazin-1-yl)methanone	IC50	0.66 nM	US-9090564: 5-alkynyl-pyridines
8-(6-methoxy-3-pyridinyl)-3-methyl-1-(oxan-4-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.668 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-[(2S)-2-hydroxypropanoyl]piperidin-4-yl]-8-(1H-indazol-4-yl)-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.721 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
4-[8-[6-(dimethylamino)-3-pyridinyl]-3-methyl-2-oxoimidazo[4,5-c][1,5]naphthyridin-1-yl]-N-methylpiperidine-1-carboxamide	KI	0.76 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
(4S)-4-(5-fluoro-6-methyl-2-pyridinyl)-3-[3-[3-fluoro-4-(1H-1,2,4-triazol-5-yl)phenyl]pyrazolo[1,5-a]pyrimidin-5-yl]-1,3-oxazolidin-2-one	IC50	0.79 nM	US-8865726: Substituted pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors
8-[6-(dimethylamino)-3-pyridinyl]-1-[1-(2-methoxyethyl)piperidin-4-yl]-3-methylimidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.802 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
methyl 4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c][1,5]naphthyridin-1-yl)piperidine-1-carboxylate	KI	0.806 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-(1-acetylpiperidin-4-yl)-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-4-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.811 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
1-[1-(2-hydroxyacetyl)piperidin-4-yl]-3-methyl-8-(1H-pyrazolo[3,4-b]pyridin-4-yl)imidazo[4,5-c][1,5]naphthyridin-2-one	KI	0.832 nM	US-8791131: Imidazo[1,5]naphthyridine compounds, their pharmaceutical use and compositions
(4S)-4-(3,4-difluorophenyl)-3-[3-[3-fluoro-4-(1H-1,2,4-triazol-5-yl)phenyl]pyrazolo[1,5-a]pyrimidin-5-yl]-1,3-oxazolidin-2-one	IC50	0.87 nM	US-8865726: Substituted pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL5420034
10.52	IC50	0.03	nM	CHEMBL5429186
10.40	IC50	0.04	nM	CHEMBL5418335
10.30	IC50	0.05	nM	SIROLIMUS
10.30	IC50	0.05	nM	EVEROLIMUS
10.22	IC50	0.06	nM	SIROLIMUS
10.22	IC50	0.06	nM	CHEMBL5420034
10.15	IC50	0.07	nM	CHEMBL3645910
10.15	IC50	0.07	nM	EVEROLIMUS
10.10	IC50	0.08	nM	CHEMBL5429186
10.10	IC50	0.08	nM	CHEMBL558955
10.04	Kd	0.092	nM	SAPANISERTIB
10.00	IC50	0.1	nM	SIROLIMUS
10.00	IC50	0.1	nM	CHEMBL5218737
10.00	IC50	0.1	nM	CHEMBL566004
10.00	IC50	0.1	nM	CHEMBL566216
10.00	IC50	0.1	nM	CHEMBL585480
10.00	IC50	0.1	nM	CHEMBL1091714
10.00	IC50	0.1	nM	CHEMBL1098245
9.96	IC50	0.11	nM	CHEMBL573157
9.93	Ki	0.117	nM	CHEMBL3681183
9.92	IC50	0.12	nM	CHEMBL604123
9.92	IC50	0.12	nM	CHEMBL600367
9.92	IC50	0.12	nM	CHEMBL600368
9.89	IC50	0.13	nM	AZD-8055
9.89	IC50	0.13	nM	CHEMBL5430111
9.85	Kd	0.14	nM	VISTUSERTIB
9.85	IC50	0.14	nM	CHEMBL5422529
9.85	IC50	0.14	nM	CHEMBL5441038
9.85	IC50	0.14	nM	VISTUSERTIB
9.85	IC50	0.14	nM	CHEMBL1091358
9.82	IC50	0.15	nM	CHEMBL3693444
9.80	IC50	0.16	nM	CHEMBL5404497
9.80	IC50	0.16	nM	CHEMBL573202
9.80	IC50	0.16	nM	CHEMBL600366
9.77	IC50	0.17	nM	RMC-5552
9.77	IC50	0.17	nM	CHEMBL578645
9.74	Ki	0.18	nM	OMIPALISIB
9.74	IC50	0.18	nM	OMIPALISIB
9.74	IC50	0.18	nM	CHEMBL1091596
9.72	IC50	0.19	nM	CHEMBL601661
9.72	IC50	0.19	nM	CHEMBL5419721
9.72	IC50	0.19	nM	CHEMBL5399980
9.72	IC50	0.19	nM	CHEMBL575976
9.72	IC50	0.19	nM	CHEMBL606423
9.70	IC50	0.2	nM	CHEMBL3577911
9.70	IC50	0.2	nM	CHEMBL3645914
9.70	IC50	0.2	nM	CHEMBL5219718
9.70	IC50	0.2	nM	CHEMBL5218916
9.70	IC50	0.2	nM	CHEMBL538378

PubChem BioAssay actives

3158 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,14,18-trihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,20-tetrone	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	<0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-12-[(2R)-1-[(1S,3R,4R)-3-methoxy-4-[4-[1-[2-[2-[2-[2-[2-[2-[2-[2-[3-[4-[4-[8-(6-methoxy-3-pyridinyl)-1-methyl-2-oxoimidazo[4,5-c]quinolin-3-yl]-2-(trifluoromethyl)phenyl]piperazin-1-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]butoxy]cyclohexyl]propan-2-yl]-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	<0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-12-[(2R)-1-[(1S,3R,4R)-3-methoxy-4-[4-[1-[2-[2-[2-[2-[2-[2-[3-[4-[4-[8-(6-methoxy-3-pyridinyl)-3-methyl-2-oxoimidazo[4,5-c]quinolin-1-yl]-2-(trifluoromethyl)phenyl]piperazin-1-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]butoxy]cyclohexyl]propan-2-yl]-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	<0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-30-[2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-30-(1,4,7,10-tetraoxacyclododec-2-ylmethoxy)-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-30-[2-(2-hydroxyethoxy)ethoxy]-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-30-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-30-[2-[2-(2-hydroxyethylsulfanyl)ethylsulfanyl]ethoxy]-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19-methoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-[4-[1-[2-[2-[2-[2-[2-[2-[2-[2-[3-[6-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]butoxy]-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0001	uM
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-14,19,30-trimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[6-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0001	uM
(1R,9S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30R,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,2R,4R,5R)-5-hydroxy-2-bicyclo[2.2.1]heptanyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1916680: Inhibition of mTORC1 in human Jurkat cells assessed as inhibition of S6K phosphorylation incubated for 4 hrs by Western blot analysis	ic50	0.0001	uM
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-14,19,30-trimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[2-[4-[7-(6-amino-3-pyridinyl)-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl]-2-fluoro-3-methylphenyl]sulfonylethylamino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0001	uM
methyl 4-[6-[4-[[4-(hydroxymethyl)phenyl]carbamoylamino]phenyl]-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	1799318: mTOR Kinase Assay from Article 10.1021/jm900851f: “ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines”	ic50	0.0001	uM
methyl 4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-[4-(pyridin-3-ylcarbamoylamino)phenyl]pyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	442311: Inhibition of FLAG-tagged human mTOR by DELFIA method	ic50	0.0001	uM
1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea	444218: Inhibition of human FLAG-tagged mTOR expressed in HEK293 cells after 2 hrs by DELFIA	ic50	0.0001	uM
3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide	1409328: Inhibition of human mTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay	kd	0.0001	uM
[5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol	1922413: Inhibition of mTOR (unknown origin)	ic50	0.0001	uM
methyl 4-[6-[4-[[4-(2-hydroxyethyl)phenyl]carbamoylamino]phenyl]-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	477628: Inhibition of human mTOR (1360-2549 amino acids) expressed in HEK293 cells	ic50	0.0001	uM
Sapanisertib	1409328: Inhibition of human mTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay	kd	0.0001	uM
1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-[4-(hydroxymethyl)phenyl]urea	444218: Inhibition of human FLAG-tagged mTOR expressed in HEK293 cells after 2 hrs by DELFIA	ic50	0.0001	uM
1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-[4-(2-hydroxyethyl)phenyl]urea	444218: Inhibition of human FLAG-tagged mTOR expressed in HEK293 cells after 2 hrs by DELFIA	ic50	0.0001	uM
1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[5,4-d]pyrimidin-6-yl]phenyl]urea	460185: Inhibition of mTOR	ic50	0.0001	uM
1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea	460185: Inhibition of mTOR	ic50	0.0001	uM
1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea	460185: Inhibition of mTOR	ic50	0.0001	uM
N-[2-(dimethylamino)ethyl]-4-[[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-(oxan-4-yl)-1,3,5-triazin-2-yl]phenyl]carbamoylamino]benzamide	473596: Inhibition of mTOR	ic50	0.0001	uM
N-[2-(dimethylamino)ethyl]-4-[[4-[4-[(3R)-3-methylmorpholin-4-yl]-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3,5-triazin-2-yl]phenyl]carbamoylamino]benzamide	473596: Inhibition of mTOR	ic50	0.0001	uM
Sirolimus	1662433: Inhibition of mTOR in HEK293 cells	ic50	0.0001	uM
Everolimus	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
2,4-difluoro-N-[2-methoxy-5-(4-pyridin-4-ylquinazolin-6-yl)-3-pyridinyl]benzenesulfonamide	1226265: Inhibition of mTOR (unknown origin) using GFP-4E-BP1 as substrate after 1 hr by TR-FRET assay	ic50	0.0002	uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(1-methylcyclobutyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assay	ic50	0.0002	uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-(2,2-dimethylbutyl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assay	ic50	0.0002	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-[4-[1-[2-[2-[2-[2-[2-[2-[2-[2-[3-[4-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]piperidin-1-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]butoxy]-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
N-[4-[4-amino-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butyl]-3-[2-[2-[2-[2-[2-[2-[2-[2-[4-[4-[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl]oxybutyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanamide	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
N-[4-[4-amino-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butyl]-3-[2-[2-[2-[2-[2-[2-[4-[4-[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl]oxybutyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanamide	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
[(1R,2R,4S)-2-methoxy-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,14,18-trihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]cyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[6-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[6-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
[(1R,2R,4S)-2-methoxy-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,14,18-trihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]cyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[2-[4-[7-(6-amino-3-pyridinyl)-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl]-2-fluoro-3-methylphenyl]sulfonylethylamino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[2-[4-[7-(6-amino-3-pyridinyl)-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl]-2-fluoro-3-methylphenyl]sulfonylethylamino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
[(1R,2R,4S)-2-methoxy-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,14,18-trihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]cyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[4-[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butylamino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0002	uM
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)-3-pyridinyl]benzenesulfonamide	1467658: Competitive inhibition of human mTOR using 4EBP1 as substrate in presence of [33gammaP]-ATP after 120 mins by filter binding method	ic50	0.0002	uM
1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-methylurea	1928553: Inhibition of human recombinant mTOR assessed as decrease in phosphorylation of S6K level at Thr389 incubated for 2 hrs in presence of ATP and His6-S6K by DELFIA assay	ic50	0.0002	uM
1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-oxocyclohexyl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]urea	460185: Inhibition of mTOR	ic50	0.0002	uM
1-[4-[1-(4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-methylurea	460185: Inhibition of mTOR	ic50	0.0002	uM
propan-2-yl 4-[6-[4-(methylcarbamoylamino)phenyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	460185: Inhibition of mTOR	ic50	0.0002	uM
1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea	442311: Inhibition of FLAG-tagged human mTOR by DELFIA method	ic50	0.0002	uM
1-(2-fluoroethyl)-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]urea	442311: Inhibition of FLAG-tagged human mTOR by DELFIA method	ic50	0.0002	uM
methyl 4-[6-[4-(methylcarbamoylamino)phenyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	442311: Inhibition of FLAG-tagged human mTOR by DELFIA method	ic50	0.0002	uM
methyl 4-[4-morpholin-4-yl-6-[4-(pyridin-3-ylcarbamoylamino)phenyl]pyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	1799318: mTOR Kinase Assay from Article 10.1021/jm900851f: “ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines”	ic50	0.0002	uM
propan-2-yl 4-[6-[4-(methylcarbamoylamino)phenyl]-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	477628: Inhibition of human mTOR (1360-2549 amino acids) expressed in HEK293 cells	ic50	0.0002	uM
1-[4-[4-morpholin-4-yl-1-(2,2,2-trifluoroethyl)pyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea	442311: Inhibition of FLAG-tagged human mTOR by DELFIA method	ic50	0.0002	uM

CTD chemical–gene interactions

386 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Sirolimus	decreases expression, affects phosphorylation, affects reaction, increases phosphorylation, decreases chemical synthesis (+10 more)	58
Resveratrol	increases reaction, affects expression, decreases activity, decreases expression, increases expression (+3 more)	15
Acetylcysteine	increases expression, decreases expression, increases phosphorylation, decreases phosphorylation, decreases reaction	15
sodium arsenite	increases phosphorylation, affects reaction, increases abundance, affects expression, increases expression (+6 more)	13
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects cotreatment, decreases reaction, increases phosphorylation, increases expression, decreases expression (+3 more)	11
dorsomorphin	increases phosphorylation, decreases phosphorylation, decreases reaction, affects cotreatment, affects phosphorylation (+1 more)	11
Cisplatin	affects phosphorylation, increases phosphorylation, increases reaction, affects cotreatment, decreases phosphorylation (+3 more)	10
bisphenol A	affects cotreatment, increases expression, increases phosphorylation, increases reaction, decreases expression (+3 more)	8
3-methyladenine	decreases phosphorylation, increases reaction, decreases expression, increases phosphorylation, decreases reaction (+2 more)	8
Estradiol	increases phosphorylation, increases reaction, affects cotreatment, decreases reaction, decreases expression (+4 more)	8
Cadmium Chloride	increases expression, decreases phosphorylation, affects reaction, decreases reaction, increases abundance (+3 more)	7
4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine	decreases reaction, decreases phosphorylation, increases expression, affects reaction, increases phosphorylation (+1 more)	6
Sorafenib	affects cotreatment, decreases activity, increases phosphorylation, decreases expression, decreases phosphorylation (+3 more)	6
Arsenic Trioxide	affects cotreatment, decreases phosphorylation, decreases reaction, increases expression, decreases expression (+1 more)	6
Cannabidiol	decreases reaction, affects cotreatment, increases expression, decreases expression, affects reaction (+1 more)	6
Niclosamide	decreases response to substance, increases phosphorylation, increases expression, decreases phosphorylation, decreases reaction	6
Oxygen	decreases reaction, increases phosphorylation, affects cotreatment, decreases phosphorylation, affects phosphorylation (+2 more)	6
Quercetin	affects cotreatment, decreases phosphorylation, decreases reaction, increases phosphorylation, increases reaction (+2 more)	6
Everolimus	affects activity, decreases response to substance, decreases activity, decreases phosphorylation, affects cotreatment (+2 more)	5
Arsenic	affects methylation, increases expression, increases reaction, decreases reaction, increases abundance (+3 more)	5
Curcumin	increases phosphorylation, decreases expression, increases expression, increases reaction, decreases phosphorylation (+1 more)	5
tetrandrine	affects cotreatment, affects expression, affects phosphorylation, decreases expression, decreases phosphorylation	4
arsenite	increases phosphorylation, affects cotreatment, decreases expression, affects binding, decreases reaction (+2 more)	4
Imatinib Mesylate	increases phosphorylation, increases reaction, decreases phosphorylation, affects cotreatment, decreases expression (+1 more)	4
Vorinostat	decreases expression, decreases activity, decreases phosphorylation	4
Air Pollutants	decreases expression, affects expression, increases abundance, affects cotreatment, decreases phosphorylation (+1 more)	4
Lipopolysaccharides	affects reaction, decreases reaction, increases phosphorylation, decreases expression, increases reaction (+1 more)	4
Paraquat	decreases expression, decreases reaction, affects expression, decreases phosphorylation	4
ochratoxin A	decreases phosphorylation, decreases reaction, decreases expression, increases phosphorylation	3
cordycepin	increases phosphorylation, affects expression, affects cotreatment, decreases phosphorylation	3

ChEMBL screening assays

1375 unique, capped per target: 1335 binding, 37 functional, 2 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4181187	Binding	Inhibition of recombinant human mTOR/FKBP12 at 10 uM by filter binding radioactive ATP transferase assay relative to control	Synthesis, antifungal and antitumor activity of two new types of imidazolin-2-ones. — Bioorg Med Chem
CHEMBL1613805	Functional	PUBCHEM_BIOASSAY: Cytometry Cell-Based qHTS for Inhibitors of the mTORC1 Signaling Pathway in MEF cells. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4612728	ADMET	Binding affinity to wild-type human partial length mTOR (L1382 to W2549 residues) expressed in mammalian expression system by Kinomescan method	Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models. — J Med Chem

Cellosaurus cell lines

22 cell lines: 19 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0844	Hs 683	Cancer cell line	Male
CVCL_3110	OVKATE	Cancer cell line	Female
CVCL_AR66	HeLa-Mitotrap	Cancer cell line	Female
CVCL_AR67	HeLa-Mitotrap-Ap1g1-FKBP	Cancer cell line	Female
CVCL_AR69	HeLa-Mitotrap-Ap2a2-FKBP	Cancer cell line	Female
CVCL_AR70	HeLa-Mitotrap-GGA2-FKBP	Cancer cell line	Female
CVCL_B0ZN	Abcam Hep-G2 MTOR KO	Cancer cell line	Male
CVCL_B3BH	Abcam HEK293T MTOR KO	Transformed cell line	Female
CVCL_D4XX	U2OS SP2 CL1	Cancer cell line	Female
CVCL_D4XY	U2OS SP2 CL2	Cancer cell line	Female

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder