MLST8

Summary

MLST8 (MTOR associated protein MLST8, HGNC:24825) is a protein-coding gene on chromosome 16p13.3, encoding Target of rapamycin complex subunit LST8 (Q9BVC4). Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. It is a selective cancer dependency (DepMap: 69.5% of cell lines).

Enables protein serine/threonine kinase activator activity and protein-macromolecule adaptor activity. Involved in TOR signaling; positive regulation of TOR signaling; and regulation of actin cytoskeleton organization. Part of TORC1 complex; TORC2 complex; and serine/threonine protein kinase complex.

Source: NCBI Gene 64223 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 49 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 69.5% of screened cell lines
• MANE Select transcript: NM_022372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24825
Approved symbol	MLST8
Name	MTOR associated protein MLST8
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Lst8, Pop3, GBL, GbetaL
Ensembl gene	ENSG00000167965
Ensembl biotype	protein_coding
OMIM	612190
Entrez	64223

Gene structure

Transcript identifiers

Ensembl transcripts: 59 — 34 protein_coding, 12 retained_intron, 8 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000301724, ENST00000382450, ENST00000397124, ENST00000561651, ENST00000562043, ENST00000562239, ENST00000562352, ENST00000562392, ENST00000562479, ENST00000562844, ENST00000562851, ENST00000563067, ENST00000563107, ENST00000563179, ENST00000564088, ENST00000564294, ENST00000564319, ENST00000564679, ENST00000565250, ENST00000565269, ENST00000565330, ENST00000565687, ENST00000565717, ENST00000565926, ENST00000566653, ENST00000566835, ENST00000567282, ENST00000567623, ENST00000567928, ENST00000568194, ENST00000568542, ENST00000569417, ENST00000569457, ENST00000569848, ENST00000570224, ENST00000878720, ENST00000878721, ENST00000878722, ENST00000878723, ENST00000878724, ENST00000878725, ENST00000878726, ENST00000878727, ENST00000878728, ENST00000878729, ENST00000878730, ENST00000878731, ENST00000878732, ENST00000878733, ENST00000878734, ENST00000878735, ENST00000878736, ENST00000878737, ENST00000878738, ENST00000945250, ENST00000945251, ENST00000945252, ENST00000945253, ENST00000945254

RefSeq mRNA: 7 — MANE Select: NM_022372 NM_001199173, NM_001199174, NM_001199175, NM_001352057, NM_001352059, NM_001352060, NM_022372

CCDS: CCDS10462, CCDS58409

Canonical transcript exons

ENST00000569417 — 9 exons

Exon	Start	End
ENSE00002613104	2205454	2205512
ENSE00002622801	2208759	2209453
ENSE00003495720	2206031	2206214
ENSE00003611614	2207035	2207110
ENSE00003616825	2207193	2207345
ENSE00003619428	2206358	2206409
ENSE00003628750	2208210	2208334
ENSE00003665527	2208450	2208613
ENSE00003693495	2206497	2206659

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.5200 / max 235.9299, expressed in 1813 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152207	30.6683	1804
152208	18.1108	1781
152210	3.9149	1472
152204	1.5100	853
152206	1.0326	627
152209	0.7036	455
152213	0.3797	196
152205	0.2001	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.10	gold quality
cerebellar hemisphere	UBERON:0002245	96.64	gold quality
cerebellar cortex	UBERON:0002129	96.56	gold quality
right frontal lobe	UBERON:0002810	95.95	gold quality
cerebellum	UBERON:0002037	95.29	gold quality
prefrontal cortex	UBERON:0000451	95.13	gold quality
anterior cingulate cortex	UBERON:0009835	95.04	gold quality
cingulate cortex	UBERON:0003027	95.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.10	gold quality
apex of heart	UBERON:0002098	93.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.73	gold quality
amygdala	UBERON:0001876	93.34	gold quality
nucleus accumbens	UBERON:0001882	93.25	gold quality
left testis	UBERON:0004533	92.95	gold quality
frontal cortex	UBERON:0001870	92.86	gold quality
neocortex	UBERON:0001950	92.85	gold quality
right lobe of thyroid gland	UBERON:0001119	92.82	gold quality
gastrocnemius	UBERON:0001388	92.81	gold quality
putamen	UBERON:0001874	92.70	gold quality
right adrenal gland cortex	UBERON:0035827	92.59	gold quality
caudate nucleus	UBERON:0001873	92.58	gold quality
right testis	UBERON:0004534	92.58	gold quality
right adrenal gland	UBERON:0001233	92.56	gold quality
mucosa of transverse colon	UBERON:0004991	92.49	gold quality
body of pancreas	UBERON:0001150	92.44	gold quality
left adrenal gland	UBERON:0001234	92.43	gold quality
left adrenal gland cortex	UBERON:0035825	92.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.33	gold quality
muscle of leg	UBERON:0001383	92.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	142.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting MLST8, 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-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-4520-5P	93.54	65.23	140

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• 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)
• Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4 (PMID:21454807)
• 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)
• MLST8 polymorphism is associated with gastric cancer. (PMID:23423739)
• The results obtained indicate that mLST8 bridges between CAD and mTOR, and plays a role in the signaling mechanism where CAD is regulated in the mTOR pathway through the association with mLST8. (PMID:23594158)
• Amino acids promote mTORC1 activation without altering Rag GTP charging. (PMID:24337580)
• MLST8 upregulation may contribute to tumor progression. (PMID:25906254)
• Data suggest MTMR3 has multiple functions in regulation of autophagy; one mechanism appears to be direct interaction between MTMR3 and mTORC1 (MTOR, mLST8, raptor) which inhibits phosphorylation activity of mTORC1; MTMR3 is localized to Golgi apparatus. (PMID:26787466)
• Autophagy regulates c-MET phosphorylation via an mTORC2-dependent mechanism. (PMID:28475179)
• NEAT1 was potentially communicated with mTOR signaling target protein mLST8 via the association with miR-181b in type 2 diabetes mellitus. (PMID:28643459)
• Enhanced mLST8 Expression Correlates with Tumor Progression in Hepatocellular Carcinoma. (PMID:32157528)
• ASO Author Reflections: mLST8 is a Prognostic Biomarker and Involved in Tumor Progression in Hepatocellular Carcinoma. (PMID:32166592)
• STAT3-mediated MLST8 gene expression regulates cap-dependent translation in cancer cells. (PMID:32495998)
• CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma. (PMID:34741373)
• Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m(6)A demethylation of EIF4EBP1 and MLST8 mRNA. (PMID:35579750)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mlst8	ENSDARG00000003167
mus_musculus	Mlst8	ENSMUSG00000024142
rattus_norvegicus	Mlst8	ENSRNOG00000009667
drosophila_melanogaster	Lst8	FBGN0264691
caenorhabditis_elegans	mlst-8	WBGENE00015697

Protein

Protein identifiers

Target of rapamycin complex subunit LST8 — Q9BVC4 (reviewed: Q9BVC4)

Alternative names: G protein beta subunit-like, Mammalian lethal with SEC13 protein 8

All UniProt accessions (11): A0A0A0MR05, Q9BVC4, H3BM50, H3BN58, H3BPT1, H3BPU5, H3BQ74, H3BR25, H3BR38, H3BSZ4, I3L2E7

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. In response to nutrients, 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 mTORC1, MLST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. As part of the mTORC2 complex, transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. 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. mTORC2 functions upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. 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 regulates the phosphorylation of SGK1 at ‘Ser-422’. mTORC2 also modulates the phosphorylation of PRKCA on ‘Ser-657’. Within mTORC2, MLST8 acts as a bridge between MAPKAP1/SIN1 and MTOR.

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 binds to and is inhibited by FKBP12-rapamycin. Within mTORC1, interacts directly with MTOR and RPTOR. Component of the mechanistic target of rapamycin complex 2 (mTORC2), consisting in two heterotretramers composed of MTOR, MLST8, RICTOR and MAPKAP1/SIN1. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. mTORC1 and mTORC2 associate with DEPTOR, which regulates their activity. Interacts with RHEB. Interacts with MEAK7. Interacts with SIK3. Interacts with SLC38A7; this interaction promotes the recruitment of mTORC1 to the lysosome and its subsequent activation.

Subcellular location. Lysosome membrane. Cytoplasm.

Tissue specificity. Broadly expressed, with highest levels in skeletal muscle, heart and kidney.

Post-translational modifications. Phosphorylation at Thr-51 by CDK1 promotes ubiquitination by the SCF(FBXW7) complex, followed by degradation. Ubiquitination by the SCF(FBXW7) and SCF(FBXW11) complexes following phosphorylation at Thr-51 by CDK1, leads to its degradation by the proteasome. Ubiquitination at Lys-305 and Lys-313 by TRAF2 via ‘Lys-63’-linked polyubiquitin chains inhibits formation of the mTORC2 complex, while promoting formation of the mTORC1 complex: ubiquitination disrupts the interaction between MLST8 and MAPKAP1/SIN1 to favor mTORC1 assembly. Deubiquitination at Lys-305 and Lys-313 by OTUD7B promotes MLST8 interaction with MAPKAP1/SIN1, facilitating mTORC2 assembly. Sumoylation with SUMO1, SUMO2 and SUMO3 promotes assembly of both mTORC1 and mTORC2 complexes.

Similarity. Belongs to the WD repeat LST8 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BVC4-1	1	yes
Q9BVC4-3	2
Q9BVC4-4	3
Q9BVC4-5	4

RefSeq proteins (7): NP_001186102, NP_001186103, NP_001186104, NP_001338986, NP_001338988, NP_001338989, NP_071767* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR037588	MLST8	Family

Pfam: PF00400

UniProt features (77 total): strand 32, mutagenesis site 11, cross-link 8, repeat 7, splice variant 5, turn 5, modified residue 4, sequence conflict 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

45 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9T94	ELECTRON MICROSCOPY	2.6
9ZBK	ELECTRON MICROSCOPY	2.6
8ERA	ELECTRON MICROSCOPY	2.86
9T93	ELECTRON MICROSCOPY	2.86
6ZWO	ELECTRON MICROSCOPY	3
9T7J	ELECTRON MICROSCOPY	3
9TDT	ELECTRON MICROSCOPY	3
5WBY	X-RAY DIFFRACTION	3.1
9T92	ELECTRON MICROSCOPY	3.1
9ED7	ELECTRON MICROSCOPY	3.16
4JSN	X-RAY DIFFRACTION	3.2
6ZWM	ELECTRON MICROSCOPY	3.2
7PE8	ELECTRON MICROSCOPY	3.2
7UXC	ELECTRON MICROSCOPY	3.2
7UXH	ELECTRON MICROSCOPY	3.2
9ZBJ	ELECTRON MICROSCOPY	3.2
6BCX	ELECTRON MICROSCOPY	3.23
9ED4	ELECTRON MICROSCOPY	3.23
7TZO	ELECTRON MICROSCOPY	3.28
4JSP	X-RAY DIFFRACTION	3.3
9TDS	ELECTRON MICROSCOPY	3.3
8RCK	ELECTRON MICROSCOPY	3.4
7PE7	ELECTRON MICROSCOPY	3.41
5WBU	X-RAY DIFFRACTION	3.42
4JT5	X-RAY DIFFRACTION	3.45
4JSV	X-RAY DIFFRACTION	3.5
4JSX	X-RAY DIFFRACTION	3.5
4JT6	X-RAY DIFFRACTION	3.6
9ED8	ELECTRON MICROSCOPY	3.61
7PEB	ELECTRON MICROSCOPY	3.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVC4-F1	92.15	0.82

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 (12): 86, 215, 245, 261, 305, 305, 313, 313, 1, 7, 1, 51

Mutagenesis-validated functional residues (11):

Position	Phenotype
44–46	in mut1; impaired assembly of the mtorc2 complex.
51	reduced ubiquitination by the scf(fbxw7) complex.
55	does not affect ubiquitination by the scf(fbxw7) complex.
72	impairs interaction with mtor.
192	abolishes interaction with mtor.
213–215	decreased sumoylation; when associated with 305-r–r-313.
272–274	in mut2; impaired assembly of the mtorc2 complex.
305–313	decreased sumoylation; when associated with 213-r–r-215.
305	elevated assembly of mtorc2 complex; when associated with r-313. decreased sumoylation.
313	elevated assembly of mtorc2 complex; when associated with r-305. decreased sumoylation.
320	impairs interaction with mtor.

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: 320 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_GROWTH, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (19): DNA damage response (GO:0006974), cytoskeleton organization (GO:0007010), negative regulation of autophagy (GO:0010507), positive regulation of cell growth (GO:0030307), positive regulation of actin filament polymerization (GO:0030838), cellular response to nutrient levels (GO:0031669), TOR signaling (GO:0031929), positive regulation of TOR signaling (GO:0032008), regulation of actin cytoskeleton organization (GO:0032956), TORC1 signaling (GO:0038202), TORC2 signaling (GO:0038203), negative regulation of apoptotic process (GO:0043066), positive regulation of glycolytic process (GO:0045821), positive regulation of lipid biosynthetic process (GO:0046889), cellular response to hypoxia (GO:0071456), cellular response to osmotic stress (GO:0071470), positive regulation of pentose-phosphate shunt (GO:1905857), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)

GO Molecular Function (3): protein-macromolecule adaptor activity (GO:0030674), protein serine/threonine kinase activator activity (GO:0043539), protein binding (GO:0005515)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), TORC1 complex (GO:0031931), TORC2 complex (GO:0031932), lysosome (GO:0005764), membrane (GO:0016020), 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	4
TOR signaling	3
cellular response to stress	2
positive regulation of intracellular signal transduction	2
TOR complex	2
organelle organization	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
response to nutrient levels	1
cellular response to stimulus	1
intracellular signal transduction	1
regulation of TOR signaling	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	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
lipid biosynthetic process	1
positive regulation of biosynthetic process	1
positive regulation of lipid metabolic process	1
regulation of lipid biosynthetic process	1
response to hypoxia	1
cellular response to decreased oxygen levels	1
response to osmotic stress	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MLST8	RICTOR	Q6R327	999
MLST8	RPTOR	Q8N122	999
MLST8	MTOR	P42345	999
MLST8	MAPKAP1	Q9BPZ7	998
MLST8	DEPTOR	Q8TB45	998
MLST8	AKT1S1	Q96B36	998
MLST8	PRR5	P85299	998
MLST8	TTI1	O43156	996
MLST8	FKBP8	Q14318	994
MLST8	PRR5L	Q6MZQ0	989
MLST8	RHEB	Q15382	984
MLST8	FKBP1A	P20071	982
MLST8	TELO2	Q9Y4R8	930
MLST8	AKT1	P31749	926
MLST8	RPS6KB1	P23443	909

IntAct

94 interactions, top by confidence:

A	B	Type	Score
MTOR	RPTOR	psi-mi:“MI:0914”(association)	0.980
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
MAPKAP1	MTOR	psi-mi:“MI:0914”(association)	0.860
MLST8	MTOR	psi-mi:“MI:0915”(physical association)	0.850
MLST8	MTOR	psi-mi:“MI:0914”(association)	0.850
AKT1S1	MTOR	psi-mi:“MI:0915”(physical association)	0.800
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
EIF4EBP1	MTOR	psi-mi:“MI:0915”(physical association)	0.660
EIF4EBP1	MTOR	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
RPTOR	MLST8	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2L	TRAPPC13	psi-mi:“MI:0914”(association)	0.560
RPS6KB1	MTOR	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
PLEKHM1	MTOR	psi-mi:“MI:0914”(association)	0.540
CLMP	UTP20	psi-mi:“MI:0914”(association)	0.530
MLST8	CCT2	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530

BioGRID (216): EIF4EBP1 (Biochemical Activity), MLST8 (Affinity Capture-Western), RPTOR (Affinity Capture-Western), MTOR (Affinity Capture-Western), MLST8 (Affinity Capture-RNA), MLST8 (Affinity Capture-RNA), MLST8 (Affinity Capture-Western), MLST8 (Affinity Capture-Western), MLST8 (Affinity Capture-MS), MLST8 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), MTOR (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT2 (Affinity Capture-MS), ACAT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EXB5, A4QNE6, A8WGF4, C1BK83, O35142, O43684, O55029, P35605, P35606, Q17QU5, Q1JP79, Q1JQB2, Q29RH4, Q29RZ9, Q3UGF1, Q4FZW5, Q4R4I8, Q561Y0, Q5I0B4, Q5M7F6, Q5MNZ6, Q5R664, Q5RB58, Q5U4Y8, Q5VQ78, Q6GNF1, Q6NWV3, Q6PA72, Q6TGU2, Q803V5, Q8AVT9, Q8BGF3, Q8IWZ6, Q8K2G4, Q8L828, Q8NEZ3, Q8VE80, Q92747, Q96J01, Q96MX6

Diamond homologs: A8Q2R5, A8XSW2, B0X2V9, B3MET8, B3NSK1, B4GIJ0, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, B7FNU7, O48716, O54927, P62883, P62884, Q05B17, Q16MY0, Q17QU5, Q1LZ08, Q20059, Q25306, Q28YY2, Q2HBX6, Q32PG3, Q4R2Z6, Q54ZP5, Q5F3K4, Q5I0B4, Q5RAW8, Q6FLI3, Q6P1V3, Q6PA72, Q6PFM9, Q6ZD63, Q7T2F6, Q803V5, Q8BH57, Q8TAF3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MLST8	“form complex”	mTORC1	binding
MLST8	“form complex”	mTORC2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Dengue virus modulates apoptosis	5	63.7×	1e-06
mTORC1-mediated signalling	5	42.5×	7e-06
Prefoldin mediated transfer of substrate to CCT/TriC	6	42.2×	7e-07
Formation of tubulin folding intermediates by CCT/TriC	5	37.8×	9e-06
Constitutive Signaling by AKT1 E17K in Cancer	5	37.8×	9e-06
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	36.4×	9e-06
Chaperonin-mediated protein folding	5	26.8×	4e-05
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	5	26.8×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	5	46.4×	8e-06
cellular response to nutrient levels	5	29.6×	7e-05
binding of sperm to zona pellucida	5	26.7×	1e-04
protein folding	10	13.1×	7e-07
positive regulation of cell growth	5	11.6×	4e-03
protein stabilization	9	7.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1510 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2206193:G:GT	donor_gain	1.0000
16:2206209:G:GT	donor_gain	1.0000
16:2206215:G:GG	donor_gain	1.0000
16:2206612:G:GT	donor_gain	1.0000
16:2206645:G:GT	donor_gain	1.0000
16:2206658:AGGT:A	donor_loss	1.0000
16:2206659:GGTGC:G	donor_loss	1.0000
16:2207341:GCACC:G	donor_gain	1.0000
16:2207342:CACC:C	donor_gain	1.0000
16:2207343:ACC:A	donor_gain	1.0000
16:2207344:CC:C	donor_gain	1.0000
16:2207345:CG:C	donor_loss	1.0000
16:2207346:G:GA	donor_loss	1.0000
16:2207346:G:GG	donor_gain	1.0000
16:2207347:T:TC	donor_loss	1.0000
16:2207348:GA:G	donor_loss	1.0000
16:2207349:AGTC:A	donor_loss	1.0000
16:2207350:G:T	donor_loss	1.0000
16:2208549:G:GT	donor_gain	1.0000
16:2208549:G:T	donor_gain	1.0000
16:2208613:GGTGA:G	donor_loss	1.0000
16:2208614:G:A	donor_loss	1.0000
16:2208614:G:GG	donor_gain	1.0000
16:2208615:T:A	donor_loss	1.0000
16:2205508:GTAAG:G	donor_loss	0.9900
16:2205512:GGT:G	donor_loss	0.9900
16:2205513:GTA:G	donor_loss	0.9900
16:2206211:CTCC:C	donor_gain	0.9900
16:2206212:TCC:T	donor_gain	0.9900
16:2206350:A:AG	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000516908 (16:2207452 C>G,T), RS1001099862 (16:2203628 A>C,G), RS1001207212 (16:2207513 G>A,C), RS1001269088 (16:2207665 C>G,T), RS1001393965 (16:2207640 A>ACACT), RS1001448421 (16:2208082 G>A), RS1001529691 (16:2207801 G>C), RS1002242191 (16:2208206 C>G), RS1002451988 (16:2204322 A>G), RS1002788518 (16:2203962 G>A,C,T), RS1003242181 (16:2209034 C>T), RS1003275110 (16:2209174 C>A,G,T), RS1003379238 (16:2205438 A>T), RS1003521928 (16:2208464 G>A), RS1003824551 (16:2204645 GAAT>G)

Disease associations

OMIM: gene MIM:612190 | disease phenotypes: MIM:308350, MIM:616044

GenCC curated gene-disease

Mondo (2): developmental and epileptic encephalopathy, 1 (MONDO:0010632), autosomal dominant nonsyndromic hearing loss 65 (MONDO:0014470)

Orphanet (1): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008163_242	Height	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4296661 (PROTEIN COMPLEX), CHEMBL4523999 (PROTEIN COMPLEX), CHEMBL6067530 (SINGLE PROTEIN)

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)

ChEMBL bioactivities

385 potent at pChembl≥5 of 387 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
9.74	IC50	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
9.52	Ki	0.3	nM	OMIPALISIB
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

PubChem BioAssay actives

400 with measured affinity, of 754 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	1871789: Inhibition of mTORC2 (unknown origin)	ic50	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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	3
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
4-phenylenediamine	decreases expression	1
sulphoraphene	decreases expression	1
bisphenol B	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects methylation, increases abundance, affects expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

275 unique, capped per target: 275 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1104625	Binding	Inhibition of mTORC1 dependent P-S6K T389 phosphorylation in human U87MG cells after 6 hrs by immunoblot	Discovery of 4-morpholino-6-aryl-1H-pyrazolo[3,4-d]pyrimidines as highly potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): optimization of the 6-aryl substituent. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1DU	Abcam HCT 116 MLST8 KO	Cancer cell line	Male
CVCL_SY55	HAP1 MLST8 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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