RPTOR

Summary

RPTOR (regulatory associated protein of MTOR complex 1, HGNC:30287) is a protein-coding gene on chromosome 17q25.3, encoding Regulatory-associated protein of mTOR (Q8N122). Component of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. It is a common-essential gene (DepMap: required in 91.9% of cancer cell lines).

This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 57521 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 165 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 91.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_020761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30287
Approved symbol	RPTOR
Name	regulatory associated protein of MTOR complex 1
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	KOG1, Mip1, KIAA1303, raptor
Ensembl gene	ENSG00000141564
Ensembl biotype	protein_coding
OMIM	607130
Entrez	57521

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000306801, ENST00000544334, ENST00000570891, ENST00000572733, ENST00000573163, ENST00000573746, ENST00000573837, ENST00000574767, ENST00000575542, ENST00000576366, ENST00000577161, ENST00000649732, ENST00000697423

RefSeq mRNA: 2 — MANE Select: NM_020761 NM_001163034, NM_020761

CCDS: CCDS11773, CCDS54175

Canonical transcript exons

ENST00000306801 — 34 exons

Exon	Start	End
ENSE00002671583	80964262	80966368
ENSE00002682664	80544838	80545791
ENSE00003464850	80962461	80962577
ENSE00003483507	80643728	80643810
ENSE00003489805	80893707	80893865
ENSE00003493588	80823079	80823223
ENSE00003499934	80730560	80730706
ENSE00003532542	80945667	80945781
ENSE00003537546	80883781	80883972
ENSE00003553829	80885008	80885148
ENSE00003562918	80925370	80925480
ENSE00003564222	80883419	80883484
ENSE00003575959	80857790	80857900
ENSE00003577292	80837922	80837997
ENSE00003594388	80922724	80922827
ENSE00003597418	80880415	80880489
ENSE00003597854	80947227	80947351
ENSE00003599440	80791450	80791509
ENSE00003600122	80822201	80822301
ENSE00003600942	80625691	80625793
ENSE00003601106	80754010	80754185
ENSE00003602199	80960078	80960205
ENSE00003617611	80908811	80908929
ENSE00003620036	80961394	80961480
ENSE00003625180	80855464	80855547
ENSE00003633181	80892729	80892869
ENSE00003635125	80891720	80891837
ENSE00003640136	80962928	80963057
ENSE00003646253	80846473	80846574
ENSE00003655832	80949443	80949547
ENSE00003672271	80923490	80923673
ENSE00003674502	80940496	80940601
ENSE00003677706	80707841	80707999
ENSE00003685592	80957624	80957730

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 89.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7352 / max 189.5829, expressed in 1809 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163253	24.5947	1808
163263	0.6602	171
163258	0.2202	54
163254	0.2194	73
163261	0.0234	8
163260	0.0123	4
163259	0.0050	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	89.43	gold quality
left ventricle myocardium	UBERON:0006566	89.15	gold quality
superficial temporal artery	UBERON:0001614	89.04	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.82	gold quality
gastrocnemius	UBERON:0001388	88.56	gold quality
stromal cell of endometrium	CL:0002255	88.13	gold quality
muscle of leg	UBERON:0001383	87.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.38	gold quality
lower esophagus	UBERON:0013473	86.37	gold quality
skeletal muscle organ	UBERON:0014892	85.92	gold quality
popliteal artery	UBERON:0002250	85.80	gold quality
tibial artery	UBERON:0007610	85.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.60	gold quality
adrenal tissue	UBERON:0018303	83.90	gold quality
bone marrow cell	CL:0002092	83.73	gold quality
apex of heart	UBERON:0002098	83.53	gold quality
prefrontal cortex	UBERON:0000451	83.49	gold quality
aorta	UBERON:0000947	83.28	gold quality
ventricular zone	UBERON:0003053	82.98	gold quality
right frontal lobe	UBERON:0002810	82.91	gold quality
right coronary artery	UBERON:0001625	82.85	gold quality
cortical plate	UBERON:0005343	82.53	gold quality
skin of leg	UBERON:0001511	82.44	gold quality
frontal cortex	UBERON:0001870	82.03	gold quality
anterior cingulate cortex	UBERON:0009835	81.91	gold quality
neocortex	UBERON:0001950	81.80	gold quality
epithelial cell of pancreas	CL:0000083	81.68	gold quality
left uterine tube	UBERON:0001303	81.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	206.98
E-GEOD-111727	no	148.34
E-ANND-3	no	4.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU2F1, RARA

miRNA regulators (miRDB)

49 targeting RPTOR, 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-7110-3P	100.00	73.18	2486
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6827-3P	98.08	72.27	651
HSA-MIR-7113-5P	97.88	67.33	1735

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels (PMID:12150925)
• raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo. (PMID:12150926)
• raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs. (PMID:12604610)
• A redox-sensitive mechanism regulates the phosphorylation of the raptor-mTOR effector S6K1, the interaction between raptor and mTOR, and the kinase activity of the raptor-mTOR complex. (PMID:16183647)
• Raptor directly binds to and serves as a scaffold for mTOR-mediated phosphorylation of IRS-1 on Ser636/639. (PMID:16354680)
• These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and in lesions associated with tuberous sclerosis. (PMID:16914728)
• These data suggest that, during HCMV infection, the rictor- and raptor-containing complexes are modified such that their substrate specificities and rapamycin sensitivities are altered. (PMID:16959881)
• ASCT2 silencing inhibits mTORC1 (mTOR/raptor) signaling and leads to growth repression, followed by enhanced survival signaling via mTORC2 (mTOR/rictor) and apoptosis of hepatoma cells. (PMID:17329400)
• Proarteriosclerotic effects of interferon gamma are associated with mammalian target of rapamycin raptor complex (mTORC1) and PI-3 kinase activiation. (PMID:17656678)
• The phosphorylation of raptor by AMPK is required for the inhibition of mTORC1 and cell-cycle arrest induced by energy stress. (PMID:18439900)
• Rag GTPases bind raptor and are necessary and sufficient to mediate amino acid signaling to mTORC1 (PMID:18497260)
• RSK-mediated phosphorylation of Raptor regulates mTORC1 activity. (PMID:18722121)
• there are two parallel cell-survival pathways in prostate cancer cells: a strong Akt-independent, but rapamycin-sensitive pathway downstream of mTORC1, and an AR-dependent pathway downstream of mTORC2 and Akt, that is stimulated by mTORC1 inhibition (PMID:18776922)
• no evidence was found for association of SNPs mapping to the NAT9, SLC9A3R1 and RAPTOR loci with susceptibility to psoriatic arthritis (PMID:19139211)
• S2448 phosphorylated mTOR binds to both raptor and rictor. (PMID:19145465)
• It has been shown that knockdown of Raptor suppresses insulin-stimulated phosphorylation of IRS-1 at Ser-636/639 and stabilizes IRS-1 after long term insulin stimulation. (PMID:19561084)
• Report involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility. (PMID:19724909)
• Complex raptor phosphorylation functions as a biochemical rheostat that modulates mTORC1 signaling in accordance with environmental cues. (PMID:19864431)
• Study demonstrates that Serine 696 and Threonine 706 represent two key sites in raptor phosphorylation during mitosis, and that the mitotic cyclin-dependent kinase cdc2/CDK1 is the kinase responsible for phosphorylating these sites. (PMID:20169205)
• These data suggest that the raptor/mTORC1 pathway may play a role in increased IRES-dependent mRNA translation during mitosis and in rapamycin insensitivity. (PMID:20439490)
• Data show that a SNP (rs11868112) 26 kb upstream to the transcription start site of RPTOR exhibiting the strongest association with temperature variables. (PMID:21060808)
• a novel regulatory mechanism by which mitogenic and oncogenic activation of the Ras/MAPK pathway promotes mTOR signaling (PMID:21071439)
• show that E2F1 is capable of inducing growth by regulating mTORC1 activity (PMID:21283628)
• results suggest that GRp58/ERp57 is involved in the assembly of mTORC1 and positively regulates mTORC1 signaling at the cytosol and the cytosolic side of the endoplasmic reticulum (PMID:21321085)
• The study identified raptor as a substrate for p44/42 MAPK. (PMID:21325048)
• Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4 (PMID:21454807)
• ULK1 contributes to mTORC1 inhibition through hindrance of substrate docking to Raptor. (PMID:21460630)
• a previously unrecognized function of miR-21 that is the reciprocal regulation of PTEN levels and Akt/TORC1 activity that mediate critical pathologic features of diabetic kidney disease (PMID:21613227)
• Phosphorylated forms of Raptor are significantly increased in mitotic cells. Raptor resides at the nucleoplasm and nucleolus of interphase cells and remains targeted to nucleolar organizer regions during mitosis. (PMID:21900751)
• An essential role of mTORC1 in autophagy inhibition in cell-free system in which, membrane association of Barkor/Atg14(L), a specific autophagosome-binding protein, is suppressed by cytosol from nutrient-rich medium, is shown. (PMID:22258093)
• an important role for ICK in modulating the activity of mTORC1 through phosphorylation of Raptor Thr-908. (PMID:22356909)
• found that osmotic stress activates mTORC1 kinase activity in a JNK-dependent manner. Our findings suggest that the molecular link between JNK and Raptor is a potential mechanism by which stress regulates the mTORC1 signaling pathway (PMID:22493283)
• Raptor polymorphism is associated with gastric cancer. (PMID:23423739)
• There is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area. (PMID:23541542)
• Single nucleotide polymorphisms in RPTOR gene is associated with obesity. (PMID:23563607)
• Histolopathological and clinical information including tumour stage, invasion characteristic and endocrine status were analysed against the gene transcript expression of mTOR, RAPTOR and RICTOR. (PMID:23898069)
• suggest no connection of RPTOR variants with psoriasis or its subphenotypes. (PMID:24005976)
• Amino acids promote mTORC1 activation without altering Rag GTP charging. (PMID:24337580)
• peptides that encompass the Raptor cross-linking region of 4E-BP1 inhibit cross-linking and interaction of 4E-BP1 with Raptor. (PMID:24403073)
• RPTOR was not associated with bipolar disorder or schizophrenia. (PMID:25053281)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rptor	ENSDARG00000098726
mus_musculus	Rptor	ENSMUSG00000025583
rattus_norvegicus	Rptor	ENSRNOG00000003821
drosophila_melanogaster	raptor	FBGN0029840
caenorhabditis_elegans		WBGENE00000911

Protein

Protein identifiers

Regulatory-associated protein of mTOR — Q8N122 (reviewed: Q8N122)

Alternative names: p150 target of rapamycin (TOR)-scaffold protein

All UniProt accessions (4): A0A8V8TMD9, Q8N122, I3L2I3, I3L436

UniProt curated annotations — full annotation on UniProt →

Function. Component of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. 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 several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy. The mTORC1 complex is inhibited in response to starvation and amino acid depletion. Within the mTORC1 complex, RPTOR acts both as a molecular adapter, which (1) mediates recruitment of mTORC1 to lysosomal membranes via interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), and a (2) substrate-specific adapter, which promotes substrate specificity by binding to TOS motif-containing proteins and direct them towards the active site of the MTOR kinase domain for phosphorylation. mTORC1 complex regulates many cellular processes, such as odontoblast and osteoclast differentiation or neuronal transmission. mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD).

Subunit / interactions. Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR. mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity. mTORC1 associates with DEPTOR, which regulates its activity. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Forms a complex with MTOR under both leucine-rich and -poor conditions. Interacts with (via TOS motifs) EIF4EBP1 and RPS6KB1; interaction is independent of its association with MTOR. Binds preferentially to poorly or non-phosphorylated forms of EIF4EBP1, and this binding is critical to the ability of MTOR to catalyze phosphorylation. Interacts with ULK1 in a nutrient-dependent manner; the interaction is reduced during starvation. Interacts with GTP-bound form of RagA/RRAGA or RagB/RRAGB and GDP-bound form of RagC/RRAGC or RagD/RRAGD, promoting recruitment of mTORC1 to the lysosomes. Interacts (when phosphorylated by AMPK) with 14-3-3 protein, leading to inhibition of its activity. Interacts with SPAG5; SPAG5 competes with MTOR for RPTOR-binding, resulting in decreased mTORC1 formation. 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 G3BP1. The complex formed with G3BP1 and SPAG5 is increased by oxidative stress. Interacts with HTR6. Interacts with PIH1D1. Interacts with LARP1. Interacts with BRAT1. Interacts with SIK3. Interacts with SLC38A7; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation. (Microbial infection) Interacts with vaccinia virus protein F17; this interaction dysregulates mTOR.

Subcellular location. Lysosome membrane. Cytoplasm. Cytoplasmic granule.

Tissue specificity. Highly expressed in skeletal muscle, and in a lesser extent in brain, lung, small intestine, kidney and placenta. Widely expressed, with highest levels in nasal mucosa and pituitary and lowest in spleen.

Post-translational modifications. Insulin-stimulated phosphorylation at Ser-863 by MTOR and MAPK8 regulates mTORC1 activity. Phosphorylated at Ser-863 by NLK in response to stress, disrupting the interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), thereby preventing lysosome recruitment and activation of the mTORC1 complex. Osmotic stress also induces phosphorylation at Ser-696, Thr-706 and Ser-863 by MAPK8. Ser-863 phosphorylation is required for phosphorylation at Ser-855 and Ser-859. In response to nutrient limitation, phosphorylated at Ser-722 and Ser-792 by AMPK; phosphorylation promotes interaction with 14-3-3 proteins, leading to negative regulation of the mTORC1 complex. Phosphorylation at Ser-722 and Ser-792 by AMPK in response to glucose starvation inhibits O-GlcNAcylation by OGT and subsequent activation of mTORC1. In response to growth factors, phosphorylated at Ser-719, Ser-721 and Ser-722 by RPS6KA1, which stimulates mTORC1 activity. Phosphorylation at Ser-791 by PKA downstream of cAMP inhibits the mTORC1 complex. Phosphorylated at Ser-877 by TBK1, leading to negative regulation of the mTORC1 complex. O-GlcNAcylated by OGT upon glucose sufficiency, promoting interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and subsequent recruitment of mTORC1 to lysosomal membranes, leading to activation of the mTORC1 complex. Phosphorylation at Ser-722 and Ser-792 by AMPK in response to glucose starvation inhibits O-GlcNAcylation. Acetylation at Lys-1097 by EP300/p300 in response to leucine metabolite acetyl-coA promotes its activity, leading to activation of the mTORC1 complex. Acetylation is decreased in response to fasting. Ubiquitinated, leading to its degradation by the proteasome. Deubiquitinated by OTUB1 via a non-catalytic mechanism. Ubiquitinated by an E3 ubiquitin ligase complex containing VHL.

Similarity. Belongs to the WD repeat RAPTOR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N122-1	1	yes
Q8N122-2	2
Q8N122-3	3, RAPTOR_v2

RefSeq proteins (2): NP_001156506, NP_065812* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000357	HEAT	Repeat
IPR001680	WD40_rpt	Repeat
IPR004083	Raptor	Family
IPR011989	ARM-like	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR029347	Raptor_N	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF02985, PF14538

UniProt features (178 total): strand 53, helix 51, mutagenesis site 23, modified residue 18, turn 16, repeat 7, compositionally biased region 2, cross-link 2, splice variant 2, chain 1, glycosylation site 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
8ERA	ELECTRON MICROSCOPY	2.86
7UX2	ELECTRON MICROSCOPY	2.9
8RCN	ELECTRON MICROSCOPY	3.1
6U62	ELECTRON MICROSCOPY	3.18
7UXC	ELECTRON MICROSCOPY	3.2
7UXH	ELECTRON MICROSCOPY	3.2
6BCX	ELECTRON MICROSCOPY	3.23
9ED4	ELECTRON MICROSCOPY	3.23
9F42	ELECTRON MICROSCOPY	3.27
8RCK	ELECTRON MICROSCOPY	3.4
9F43	ELECTRON MICROSCOPY	3.49
7PEB	ELECTRON MICROSCOPY	3.67
9F44	ELECTRON MICROSCOPY	3.68
9F45	ELECTRON MICROSCOPY	3.74
6BCU	ELECTRON MICROSCOPY	3.8
8RCH	ELECTRON MICROSCOPY	4
7PEA	ELECTRON MICROSCOPY	4.07
7PEC	ELECTRON MICROSCOPY	4.24
5H64	ELECTRON MICROSCOPY	4.4
7OWG	ELECTRON MICROSCOPY	4.7
6SB0	ELECTRON MICROSCOPY	5.5
6SB2	ELECTRON MICROSCOPY	6.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N122-F1	80.67	0.60

Functional residue map

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

Post-translational modifications (20): 44, 122, 696, 706, 719, 721, 722, 738, 791, 792, 836, 855, 859, 863, 865, 877, 982, 1097, 932, 948

Glycosylation sites (1): 700

Mutagenesis-validated functional residues (23):

Position	Phenotype
557–564	in alpha24 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes.
560	in alphax3 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes; when associated with e-597 a
594–598	in alpha26 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes.
597	in alphax3 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes; when associated with f-560 a
634–636	in alpha29 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes.
635	in alphax3 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes; when associated with f-560 a
699	does not affect o-glcnacylation in response to glucose sufficiency.
700	abolished o-glcnacylation in response to glucose sufficiency, leading to decreased mtorc1 activation.
722	abolishes ampk-mediated phosphorylation; when associated with a-792. increased o-glcnacylation; when associated with a-7
737	does not affect ubiquitination.
791	abolished phosphorylation after forskolin treatment.
792	abolishes ampk-mediated phosphorylation; when associated with a-722. increased o-glcnacylation; when associated with a-7
863	abolished phosphorylation by nlk, leading to impaired inhibition of the mtorc1 complex in response to osmotic stress.
863	mimics phosphorylation, leading to impaired interaction with small gtpases rag and activation of the mtorc1 complex.
877	decreased phosphorylation, leading to increased activity of the mtorc1 complex.
894	does not affect ubiquitination.
916–936	in clw1 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes without affecting the compositio
919–921	in clw2 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes without affecting the compositio
925–928	in clw3 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes without affecting the compositio
932	decreased ubiquitination.
933–935	in clw4 mutant; abolished interaction with gtp-bound rraga and recruitment to lysosomes without affecting the compositio
948	decreased ubiquitination.
1097	reduced acetylation, leading to decreased activation of the mtorc complex.

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
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-5628897	TP53 Regulates Metabolic Genes
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-9920951	Dengue virus modulates apoptosis
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3371556	Cellular response to heat stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9612973	Autophagy
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 347 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_VACUOLAR_MEMBRANE, GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING

GO Biological Process (35): regulation of cell growth (GO:0001558), positive regulation of endothelial cell proliferation (GO:0001938), DNA damage response (GO:0006974), regulation of cell size (GO:0008361), cellular response to starvation (GO:0009267), response to xenobiotic stimulus (GO:0009410), regulation of autophagy (GO:0010506), negative regulation of autophagy (GO:0010507), positive regulation of cell growth (GO:0030307), cellular response to nutrient levels (GO:0031669), TOR signaling (GO:0031929), positive regulation of TOR signaling (GO:0032008), social behavior (GO:0035176), TORC1 signaling (GO:0038202), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of glycolytic process (GO:0045821), positive regulation of transcription by RNA polymerase III (GO:0045945), positive regulation of lipid biosynthetic process (GO:0046889), cellular response to amino acid stimulus (GO:0071230), cellular response to L-leucine (GO:0071233), cellular response to glucose stimulus (GO:0071333), cellular response to hypoxia (GO:0071456), cellular response to osmotic stress (GO:0071470), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of odontoblast differentiation (GO:1901331), positive regulation of pentose-phosphate shunt (GO:1905857), autophagosome assembly (GO:0000045), cytoplasmic translation (GO:0002181), regulation of cell communication (GO:0010646), regulation of signaling (GO:0023051), negative regulation of translational initiation (GO:0045947), positive regulation of translational initiation (GO:0045948), protein localization to lysosome (GO:0061462), regulation of biological quality (GO:0065008), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (9): protein kinase binding (GO:0019901), protein serine/threonine kinase inhibitor activity (GO:0030291), protein kinase activator activity (GO:0030295), protein-macromolecule adaptor activity (GO:0030674), small GTPase binding (GO:0031267), protein-containing complex binding (GO:0044877), 14-3-3 protein binding (GO:0071889), enzyme-substrate adaptor activity (GO:0140767), protein binding (GO:0005515)

GO Cellular Component (11): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), dendrite (GO:0030425), TORC1 complex (GO:0031931), neuronal cell body (GO:0043025), membrane (GO:0016020), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Signal Transduction	2
MTOR signalling	2
Autophagy	1
Cellular response to heat stress	1
Transcriptional Regulation by TP53	1
PTEN Regulation	1
Cellular response to starvation	1
Dengue Virus-Host Interactions	1
Intracellular signaling by second messengers	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Generic Transcription Pathway	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell growth	2
cellular response to stress	2
autophagy	2
TOR signaling	2
protein binding	2
binding	2
regulation of growth	1
regulation of cellular component organization	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of cellular component size	1
cellular response to nutrient levels	1
response to starvation	1
response to chemical	1
regulation of catabolic process	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
response to nutrient levels	1
cellular response to stimulus	1
intracellular signal transduction	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
positive regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
glycolytic process	1
regulation of glycolytic process	1
positive regulation of purine nucleotide catabolic process	1
positive regulation of carbohydrate metabolic process	1
positive regulation of ATP metabolic process	1
regulation of transcription by RNA polymerase III	1
transcription by RNA polymerase III	1
positive regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

3272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPTOR	RPS6KB1	P23443	999
RPTOR	RICTOR	Q6R327	999
RPTOR	MTOR	P42345	999
RPTOR	AKT1S1	Q96B36	999
RPTOR	MLST8	Q9BVC4	999
RPTOR	RHEB	Q15382	998
RPTOR	DEPTOR	Q8TB45	998
RPTOR	EIF4EBP1	Q13541	997
RPTOR	FKBP1A	P20071	996
RPTOR	RRAGB	Q5VZM2	995
RPTOR	RRAGA	Q7L523	995
RPTOR	FKBP8	Q14318	994
RPTOR	TTI1	O43156	993
RPTOR	MAPKAP1	Q9BPZ7	992
RPTOR	RRAGC	Q9HB90	990

IntAct

265 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
MTOR	RICTOR	psi-mi:“MI:0915”(physical association)	0.970
RICTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.970
MTOR	RICTOR	psi-mi:“MI:0914”(association)	0.970
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960

BioGRID (673): RPTOR (Affinity Capture-Western), MTOR (Affinity Capture-Western), AKT1S1 (Affinity Capture-Western), RPTOR (Affinity Capture-Western), CHUK (Affinity Capture-Western), IKBKB (Affinity Capture-Western), IKBKG (Affinity Capture-Western), MTOR (Affinity Capture-Western), RPTOR (Co-purification), MTOR (Affinity Capture-Western), AKT1S1 (Affinity Capture-Western), RPTOR (Affinity Capture-Western), RPTOR (Reconstituted Complex), RPTOR (Affinity Capture-Western), RPTOR (Affinity Capture-Western)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: C7J8E5, P38873, P87141, Q0DJA3, Q0IQN5, Q55BR7, Q8K4Q0, Q8N122, Q93YQ1, Q9LZW9, B7E321, O04492, P51833, Q0DKP4, Q0IQN6, Q0IV63, Q16AI6, Q47S78, Q5N8Z0, Q6YW64, Q82JT9, Q8GY79, Q8H1D4, Q9AV50, Q9LJF5, Q9SKN2, Q9ZBQ7

SIGNOR signaling

38 interactions.

A	Effect	B	Mechanism
RRAGC	up-regulates	RPTOR	binding
RRAGD	up-regulates	RPTOR	binding
CDK1	unknown	RPTOR	phosphorylation
MAPK1	unknown	RPTOR	phosphorylation
MAPK3	“up-regulates activity”	RPTOR	phosphorylation
PRKAA1	“down-regulates activity”	RPTOR	phosphorylation
PRKAB1	down-regulates	RPTOR	phosphorylation
MAPK11	unknown	RPTOR	phosphorylation
ERK1/2	“up-regulates activity”	RPTOR	phosphorylation
MTOR	“up-regulates activity”	RPTOR	phosphorylation
RPS6KA1	up-regulates	RPTOR	phosphorylation
MAPK1	“up-regulates activity”	RPTOR	phosphorylation
CILK1	up-regulates	RPTOR	phosphorylation
RPTOR	“form complex”	mTORC1	binding
RPS6K	up-regulates	RPTOR	phosphorylation
Gbeta	“up-regulates activity”	RPTOR	phosphorylation
NLK	“down-regulates activity”	RPTOR	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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	14	59.0×	4e-20
Energy dependent regulation of mTOR by LKB1-AMPK	11	38.3×	2e-13
Activation of BAD and translocation to mitochondria	5	33.7×	6e-06
MTOR signalling	14	32.9×	8e-16
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	29.7×	1e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	29.7×	1e-05
Cellular response to heat stress	8	27.9×	1e-08
Activation of BH3-only proteins	6	26.4×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
TORC1 signaling	8	42.0×	2e-09
positive regulation of TOR signaling	10	32.4×	2e-10
cellular response to nutrient levels	9	27.5×	6e-09
positive regulation of TORC1 signaling	12	23.2×	1e-10
cellular response to amino acid stimulus	11	22.0×	8e-10
cellular response to amino acid starvation	8	16.6×	4e-06
negative regulation of autophagy	8	13.6×	2e-05
negative regulation of TORC1 signaling	6	12.7×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

10977 predictions. Top by Δscore:

Variant	Effect	Δscore
17:80625677:T:A	acceptor_gain	1.0000
17:80625680:T:A	acceptor_gain	1.0000
17:80625682:T:TA	acceptor_gain	1.0000
17:80625686:TTCA:T	acceptor_loss	1.0000
17:80625687:TCAG:T	acceptor_loss	1.0000
17:80625688:CAG:C	acceptor_loss	1.0000
17:80625689:A:AG	acceptor_gain	1.0000
17:80625689:A:G	acceptor_loss	1.0000
17:80625689:AGAT:A	acceptor_gain	1.0000
17:80625690:G:GA	acceptor_gain	1.0000
17:80625690:GA:G	acceptor_gain	1.0000
17:80625690:GAT:G	acceptor_gain	1.0000
17:80625690:GATG:G	acceptor_gain	1.0000
17:80625690:GATGA:G	acceptor_gain	1.0000
17:80625789:GATCG:G	donor_gain	1.0000
17:80625790:ATCG:A	donor_gain	1.0000
17:80625791:TCG:T	donor_gain	1.0000
17:80625792:CGGTG:C	donor_loss	1.0000
17:80625794:G:GG	donor_gain	1.0000
17:80625795:T:A	donor_loss	1.0000
17:80643809:GG:G	donor_gain	1.0000
17:80643810:GG:G	donor_gain	1.0000
17:80707833:T:A	acceptor_gain	1.0000
17:80707836:A:AG	acceptor_gain	1.0000
17:80707836:AACAG:A	acceptor_gain	1.0000
17:80707837:A:G	acceptor_gain	1.0000
17:80707838:CAGGC:C	acceptor_loss	1.0000
17:80707839:A:AG	acceptor_gain	1.0000
17:80707839:AG:A	acceptor_gain	1.0000
17:80707839:AGGC:A	acceptor_loss	1.0000

AlphaMissense

8804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:80545774:T:A	W49R	1.000
17:80545774:T:C	W49R	1.000
17:80545776:G:C	W49C	1.000
17:80545776:G:T	W49C	1.000
17:80545778:G:C	R50T	1.000
17:80545778:G:T	R50M	1.000
17:80545779:G:C	R50S	1.000
17:80545779:G:T	R50S	1.000
17:80625694:A:G	K56E	1.000
17:80625696:G:C	K56N	1.000
17:80625696:G:T	K56N	1.000
17:80625698:C:A	T57K	1.000
17:80625698:C:G	T57R	1.000
17:80625698:C:T	T57I	1.000
17:80625703:A:C	S59R	1.000
17:80625705:T:A	S59R	1.000
17:80625705:T:G	S59R	1.000
17:80625707:T:A	V60D	1.000
17:80625710:C:A	A61D	1.000
17:80625721:T:C	C65R	1.000
17:80625722:G:A	C65Y	1.000
17:80625723:C:G	C65W	1.000
17:80625725:T:C	L66P	1.000
17:80625787:T:A	W87R	1.000
17:80625787:T:C	W87R	1.000
17:80643799:T:A	W113R	1.000
17:80643799:T:C	W113R	1.000
17:80643809:G:C	R116T	1.000
17:80643809:G:T	R116M	1.000
17:80643810:G:C	R116S	1.000

dbSNP variants (sampled 300 via entrez): RS1000009452 (17:80606736 A>G,T), RS1000013745 (17:80602708 C>A,G), RS1000019348 (17:80795778 A>G), RS1000024292 (17:80890823 C>A,T), RS1000025847 (17:80931303 A>T), RS1000025880 (17:80720953 C>G), RS1000026583 (17:80750184 C>T), RS1000030474 (17:80676279 G>A), RS1000033648 (17:80612912 T>A), RS1000033974 (17:80958950 G>C), RS1000038335 (17:80955257 A>G), RS1000040560 (17:80594822 G>A), RS1000050346 (17:80632660 C>T), RS1000052843 (17:80791277 A>G,T), RS1000067737 (17:80601482 C>T)

Disease associations

OMIM: gene MIM:607130 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001712_60	Myopia (pathological)	2.000000e-06
GCST001953_27	Obesity	2.000000e-08
GCST002724_26	Airway responsiveness in chronic obstructive pulmonary disease	9.000000e-06
GCST002783_371	Body mass index	4.000000e-10
GCST002783_504	Body mass index	2.000000e-09
GCST002783_97	Body mass index	5.000000e-07
GCST004495_117	BMI (adjusted for smoking behaviour)	7.000000e-07
GCST004495_118	BMI (adjusted for smoking behaviour)	2.000000e-08
GCST004497_1	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-06
GCST004497_140	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-07
GCST004499_48	BMI in non-smokers	2.000000e-06
GCST004499_49	BMI in non-smokers	5.000000e-07
GCST004904_193	Body mass index	6.000000e-09
GCST006009_2	Pulse pressure	3.000000e-10
GCST007703_101	Systolic blood pressure	9.000000e-12
GCST007705_77	Pulse pressure	3.000000e-13
GCST007706_11	Mean arterial pressure	1.000000e-06
GCST007707_106	Hypertension	8.000000e-09
GCST008103_158	Bipolar disorder	6.000000e-06
GCST009548_3	NASH resolution in nonalcoholic steatohepatitis	5.000000e-06
GCST009600_80	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-08
GCST010105_140	Nicotine dependence symptom count	4.000000e-06
GCST010988_68	Adult body size	9.000000e-21
GCST010989_276	Body size at age 10	8.000000e-16

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0006897	airway responsiveness measurement
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0009785	remission
EFO:0009262	nicotine dependence symptom count
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3120040 (SINGLE PROTEIN), CHEMBL4296661 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 272,930 (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
CHEMBL1908360	EVEROLIMUS	4	73,430
CHEMBL413	SIROLIMUS	4	172,798
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL1236962	OMIPALISIB	2	3,989
CHEMBL2336325	VISTUSERTIB	2	1,961
CHEMBL3120215	OSI-027	2	1,854
CHEMBL3545097	SAPANISERTIB	2	2,524
CHEMBL3586404	ONATASERTIB	2	1,091
CHEMBL3586573	CC-115	2	1,240
CHEMBL3813842	PAXALISIB	2	1,078
CHEMBL4084907	BIMIRALISIB	2	1,625
CHEMBL1801204	AZD-8055	1	3,350
CHEMBL5314926	RMC-5552	1	2

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9906827	Efficacy,Toxicity	3	everolimus	Pneumonitis;Progression-free survival

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9906827	RPTOR	3	5.00	1	everolimus

ChEMBL bioactivities

258 potent at pChembl≥5 of 260 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	EVEROLIMUS
10.10	IC50	0.08	nM	CHEMBL5429186
10.00	IC50	0.1	nM	CHEMBL5218737
9.89	IC50	0.13	nM	CHEMBL5430111
9.85	IC50	0.14	nM	CHEMBL5422529
9.85	IC50	0.14	nM	CHEMBL5441038
9.80	IC50	0.16	nM	CHEMBL5404497
9.77	IC50	0.17	nM	RMC-5552
9.74	Ki	0.18	nM	OMIPALISIB
9.72	IC50	0.19	nM	CHEMBL5419721
9.72	IC50	0.19	nM	CHEMBL5399980
9.70	IC50	0.2	nM	CHEMBL5219718
9.70	IC50	0.2	nM	CHEMBL5218916
9.66	IC50	0.22	nM	CHEMBL5430354
9.64	IC50	0.23	nM	CHEMBL5413401
9.62	IC50	0.24	nM	CHEMBL5408375
9.62	IC50	0.24	nM	CHEMBL5422229
9.60	EC50	0.25	nM	CHEMBL1765602
9.59	IC50	0.26	nM	CHEMBL5404617
9.57	IC50	0.27	nM	CHEMBL5427995
9.55	IC50	0.28	nM	CHEMBL5440792
9.54	IC50	0.29	nM	CHEMBL5394998
9.54	IC50	0.29	nM	TORIN1
9.43	IC50	0.37	nM	CHEMBL5419762
9.43	IC50	0.37	nM	CHEMBL5431157
9.38	IC50	0.42	nM	CHEMBL5422165
9.38	IC50	0.42	nM	CHEMBL5419721
9.36	IC50	0.44	nM	CHEMBL5430111
9.36	IC50	0.44	nM	CHEMBL5441038
9.33	IC50	0.47	nM	CHEMBL5425648
9.32	IC50	0.48	nM	CHEMBL5422529
9.31	IC50	0.49	nM	CHEMBL5434290
9.30	IC50	0.5	nM	CHEMBL5218727
9.23	IC50	0.59	nM	CHEMBL5416606
9.21	IC50	0.61	nM	CHEMBL5418134
9.17	IC50	0.67	nM	CHEMBL5404497
9.16	IC50	0.69	nM	SAPANISERTIB
9.15	IC50	0.7	nM	CHEMBL2334767
9.15	IC50	0.7	nM	CHEMBL5218590
9.15	IC50	0.7	nM	CHEMBL5220152
9.15	IC50	0.7	nM	CHEMBL5413401
9.10	IC50	0.8	nM	AZD-8055
9.06	IC50	0.87	nM	CHEMBL5220536

PubChem BioAssay actives

274 with measured affinity, of 498 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
Sirolimus	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	uM
Everolimus	1916668: Inhibition of mTORC1 (unknown origin)	ic50	0.0001	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	1994264: Inhibition of mTORC1 (unknown origin) assessed as inhibition constant	ki	0.0002	uM
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,32S,35R)-1,18-dihydroxy-30-(2-hydroxyethoxy)-19-methoxy-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-phenylethyl)carbamate	1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assay	ic50	0.0003	uM
N-[4-[4-amino-3-(5-hydroxy-1H-indol-2-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	0.0003	uM
N-[4-[4-amino-3-(2-amino-1,3-benzoxazol-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	0.0003	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,32S,35R)-1,18-dihydroxy-30-(2-hydroxyethoxy)-19-methoxy-12-[(2R)-1-[(1S,3R,4R)-3-methoxy-4-[3-[(3S)-3-methylmorpholin-4-yl]propoxy]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	1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assay	ic50	0.0003	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-[3-[(2S,6R)-2,6-dimethylmorpholin-4-yl]propoxy]-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-30-(2-hydroxyethoxy)-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	1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assay	ic50	0.0003	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,32S,35R)-1,18-dihydroxy-30-(2-hydroxyethoxy)-19-methoxy-12-[(2R)-1-[(1S,3R,4R)-3-methoxy-4-[3-[(3R)-3-methylmorpholin-4-yl]propoxy]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	1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assay	ic50	0.0003	uM
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-[3-(2,2-dimethylmorpholin-4-yl)propoxy]-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-30-(2-hydroxyethoxy)-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	1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assay	ic50	0.0003	uM
N-[4-[3-(2-amino-1,3-benzoxazol-5-yl)-4-(dimethylamino)pyrazolo[5,4-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	0.0003	uM
8-(6-methoxy-3-pyridinyl)-1-methyl-3-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]imidazo[4,5-c]quinolin-2-one	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0003	uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one	1994242: Inhibition of mTORC1 (unknown origin)	ic50	0.0003	uM
9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one	1512676: Inhibition of mTORC1 in human HCT116 cells assessed as reduction in T389 phosphorylation on RPS6KB1 after 1 hr by Western blot analysis	ec50	0.0003	uM
(1R,9S,12S,14R,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]-14,19,30-trimethoxy-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	0.0004	uM
N-[4-[4-amino-3-(2-amino-1,3-benzoxazol-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	0.0004	uM
N-[4-[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butyl]-3-[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]propanamide	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0004	uM
N-[4-[4-amino-3-(5-hydroxy-1H-indol-2-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butyl]-3-[2-[2-[2-[2-[2-[2-[2-[2-[4-[2-[(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]oxyethoxymethyl]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	0.0005	uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]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	0.0005	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-[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	0.0005	uM
N-[4-[4-amino-3-(5-hydroxy-1H-indol-2-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	0.0006	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-[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	0.0006	uM
N-[5-[4,6-diamino-1-(2,2-dimethylbutyl)pyrazolo[3,4-d]pyrimidin-3-yl]-1,3-benzoxazol-2-yl]acetamide	1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assay	ic50	0.0007	uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-(2,2-dimethylpropyl)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	0.0007	uM
Sapanisertib	1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay	ic50	0.0007	uM
2-[(1R,9S)-4-[4-(ethylcarbamoylamino)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]-3,5,12-triazatricyclo[7.2.1.02,7]dodeca-2(7),3,5-trien-12-yl]-N,2-dimethylpropanamide	730846: Inhibition of mTORC1 in human NCI-PC3 cells assessed as inhibition of p70S6K phosphorylation	ic50	0.0007	uM
[5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol	1512672: Inhibition of mTORC1 (unknown origin)	ic50	0.0008	uM
N-[4-[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butyl]-3-[2-[2-[2-[2-[2-[2-[2-[2-[4-[2-[(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]oxyethoxymethyl]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	0.0009	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	5
Sirolimus	increases expression, decreases phosphorylation, decreases activity, decreases reaction, increases activity (+1 more)	4
Air Pollutants	affects methylation, affects cotreatment, decreases expression, increases abundance, increases expression	3
Valproic Acid	increases methylation	3
bisphenol A	affects methylation, affects cotreatment, increases methylation, decreases expression	2
bisphenol S	affects cotreatment, increases methylation, decreases expression, affects methylation	2
Zoledronic Acid	decreases expression	2
Cisplatin	decreases expression	2
Dexamethasone	affects cotreatment, increases phosphorylation, decreases expression	2
Aflatoxin B1	affects methylation, decreases expression	2
FR900359	affects phosphorylation	1
4-nitrochalcone	decreases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
naringenin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
lead acetate	decreases phosphorylation, increases abundance, affects reaction	1
decabromobiphenyl ether	decreases expression	1
ascorbate-2-phosphate	affects cotreatment, increases phosphorylation	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
tetrathiomolybdate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
oxophenylarsine	affects binding, decreases reaction, increases phosphorylation	1
4-phenylenediamine	decreases expression	1

ChEMBL screening assays

183 unique, capped per target: 183 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3124153	Binding	Binding affinity to raptor in human SQ20B cells after 10 to 12 hrs by pull down assay	Benzofuran derivatives as a novel class of inhibitors of mTOR signaling. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1K2	HyCyte HCT 116 KO-hRPTOR	Cancer cell line	Male

Clinical trials (associated diseases)

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