Send feedback

MLST8

gene
On this page

Also known as Lst8Pop3GBLGbetaL

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. Contributes to protein serine/threonine kinase activity. Involved in TOR signaling; positive regulation of TOR signaling; and regulation of actin cytoskeleton organization. Part of TORC1 complex and TORC2 complex.

Source: NCBI Gene 64223 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 48 total
  • GTEx eGene: eQTL in 48 tissues, sQTL in 50 (q < 0.05)
  • Drug target: yes — 1 via a complex or family; 13 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
  • Cancer dependency (DepMap): dependent in 69.5% of screened cell lines
  • Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 0.68 (unconstrained)
  • MANE Select transcript: NM_022372

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24825
Approved symbolMLST8
NameMTOR associated protein MLST8
Location16p13.3
Locus typegene with protein product
StatusApproved
AliasesLst8, Pop3, GBL, GbetaL
Ensembl geneENSG00000167965
Ensembl biotypeprotein_coding
OMIM612190
Entrez64223

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 39 protein_coding, 37 nonsense_mediated_decay, 12 retained_intron, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000569417

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 11, TSL 3: 6, TSL 4: 8, TSL 5: 6

ENST00000569417, 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, 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, ENST00001008646, ENST00001008648, ENST00001008649, ENST00001008650, ENST00001008651, ENST00001008652, ENST00001008653, ENST00001037921, ENST00001037922, ENST00001037923, ENST00001037924, ENST00001037925, ENST00001037926, ENST00001037927, ENST00001037928, ENST00001037929, ENST00001037930, ENST00001037931, ENST00001037932, ENST00001037933, ENST00001037934, ENST00001037935, ENST00001082229, ENST00001082230, ENST00001082231, ENST00001082232, ENST00001082233, ENST00001082234, ENST00001082235, ENST00001082236, ENST00001082237, ENST00001098771, ENST00001112993, ENST00001133167

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

ExonStartEnd
ENSE0000261310422054542205512
ENSE0000349572022060312206214
ENSE0000361161422070352207110
ENSE0000361682522071932207345
ENSE0000361942822063582206409
ENSE0000362875022082102208334
ENSE0000366552722084502208613
ENSE0000369349522064972206659
ENSE0000478217222087592209453

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.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, frontal lobe, cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MLST8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 48 tissues and its splicing (sQTL) in 50 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 98 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Muscle Skeletalsqtl1.4e-99-1.0116:2205221:C:T
Cells Cultured fibroblastseqtl8.9e-96+0.6716:2205762:A:C
Thyroidsqtl1.4e-78-0.9116:2206046:AC:A
Cells Cultured fibroblastssqtl3.7e-72-1.0116:2206325:C:T
Skin Sun Exposed Lower legsqtl1.2e-62-0.8916:2206046:AC:A
Skin Not Sun Exposed Suprapubicsqtl6.9e-60-0.9116:2205221:C:T
Thyroideqtl2.0e-59+0.3716:2206460:C:G
Testissqtl8.8e-52-1.0616:2206046:AC:A
Esophagus Mucosasqtl5.3e-49-0.9316:2206325:C:T
Nerve Tibialsqtl7.1e-49-0.8316:2206046:AC:A
Adipose Subcutaneoussqtl2.3e-48-0.8016:2205221:C:T
Cells EBV-transformed lymphocytessqtl6.0e-41-1.0616:2206046:AC:A
Brain Cerebellumsqtl1.3e-40-1.1216:2207104:C:G
Brain Cerebellar Hemispheresqtl5.8e-39-1.0616:2207104:C:G
Nerve Tibialeqtl7.3e-39+0.3116:2205221:C:T
Artery Tibialeqtl1.2e-38+0.3016:2206046:AC:A
Whole Bloodsqtl2.0e-38-0.7316:2207104:C:G
Breast Mammary Tissuesqtl2.8e-38-0.8516:2206046:AC:A
Skin Sun Exposed Lower legeqtl6.4e-38+0.2216:2205221:C:T
Skin Not Sun Exposed Suprapubiceqtl2.7e-37+0.2716:2205221:C:T

FANTOM5 promoters

8 alternative TSS:

Promoter IDTPM avgSamples expressed
15220730.66831804
15220818.11081781
1522103.91491472
1522041.5100853
1522061.0326627
1522090.7036455
1522130.3797196
1522050.200197

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right hemisphere of cerebellumUBERON:001489097.10gold quality
cerebellar hemisphereUBERON:000224596.64gold quality
cerebellar cortexUBERON:000212996.56gold quality
right frontal lobeUBERON:000281095.95gold quality
cerebellumUBERON:000203795.29gold quality
prefrontal cortexUBERON:000045195.13gold quality
anterior cingulate cortexUBERON:000983595.04gold quality
cingulate cortexUBERON:000302795.02gold quality
hindlimb stylopod muscleUBERON:000425294.10gold quality
apex of heartUBERON:000209893.80gold quality
Brodmann (1909) area 9UBERON:001354093.73gold quality
amygdalaUBERON:000187693.34gold quality
nucleus accumbensUBERON:000188293.25gold quality
left testisUBERON:000453392.95gold quality
frontal cortexUBERON:000187092.86gold quality
neocortexUBERON:000195092.85gold quality
right lobe of thyroid glandUBERON:000111992.82gold quality
gastrocnemiusUBERON:000138892.81gold quality
putamenUBERON:000187492.70gold quality
right adrenal gland cortexUBERON:003582792.59gold quality
caudate nucleusUBERON:000187392.58gold quality
right testisUBERON:000453492.58gold quality
right adrenal glandUBERON:000123392.56gold quality
mucosa of transverse colonUBERON:000499192.49gold quality
body of pancreasUBERON:000115092.44gold quality
left adrenal glandUBERON:000123492.43gold quality
left adrenal gland cortexUBERON:003582592.34gold quality
C1 segment of cervical spinal cordUBERON:000646992.33gold quality
muscle of legUBERON:000138392.28gold quality
dorsolateral prefrontal cortexUBERON:000983492.13gold quality
left lobe of thyroid glandUBERON:000112091.92gold quality
adenohypophysisUBERON:000219691.60gold quality
adrenal cortexUBERON:000123591.47gold quality
right uterine tubeUBERON:000130291.20gold quality
spinal cordUBERON:000224091.14gold quality
body of stomachUBERON:000116191.13gold quality
thyroid glandUBERON:000204691.07gold quality
metanephros cortexUBERON:001053391.02gold quality
telencephalonUBERON:000189391.01gold quality
cerebral cortexUBERON:000095690.99gold quality
brainUBERON:000095590.95gold quality
testisUBERON:000047390.94gold quality
ganglionic eminenceUBERON:000402390.84gold quality
forebrainUBERON:000189090.81gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099190.80gold quality
stromal cell of endometriumCL:000225590.73gold quality
right lobe of liverUBERON:000111490.59gold quality
pituitary glandUBERON:000000790.51gold quality
hypothalamusUBERON:000189890.49gold quality
granulocyteCL:000009490.37gold quality
skin of legUBERON:000151190.11gold quality
adrenal glandUBERON:000236990.09gold quality
skin of abdomenUBERON:000141689.88gold quality
right atrium auricular regionUBERON:000663189.87gold quality
left ovaryUBERON:000211989.81gold quality
ventricular zoneUBERON:000305389.78gold quality
lower esophagus mucosaUBERON:003583489.69gold quality
transverse colonUBERON:000115789.68gold quality
esophagus mucosaUBERON:000246989.67gold quality
Ammon’s hornUBERON:000195489.64gold quality
heart left ventricleUBERON:000208489.63gold quality
right ovaryUBERON:000211889.53gold quality
minor salivary glandUBERON:000183089.49gold quality
small intestine Peyer’s patchUBERON:000345489.40gold quality
esophagogastric junction muscularis propriaUBERON:003584189.40gold quality
skeletal muscle organUBERON:001489289.20gold quality
muscle organUBERON:000163089.19gold quality
cardiac ventricleUBERON:000208289.07gold quality
body of uterusUBERON:000985389.07gold quality
esophagusUBERON:000104389.06gold quality
muscle layer of sigmoid colonUBERON:003580588.95gold quality
cortical plateUBERON:000534388.92gold quality
lower esophagusUBERON:001347388.90gold quality
lower esophagus muscularis layerUBERON:003583388.90gold quality
spleenUBERON:000210688.64gold quality
stomachUBERON:000094588.55gold quality
left uterine tubeUBERON:000130388.47gold quality
left coronary arteryUBERON:000162688.44gold quality
cardiac atriumUBERON:000208188.42gold quality
substantia nigraUBERON:000203888.41gold quality
gall bladderUBERON:000211088.40gold quality
type B pancreatic cellCL:000016988.37gold quality
temporal lobeUBERON:000187188.32gold quality
ectocervixUBERON:001224988.23gold quality
pancreasUBERON:000126488.17gold quality
upper lobe of left lungUBERON:000895288.14gold quality
tibial nerveUBERON:000132388.13gold quality
endocervixUBERON:000045888.05gold quality
olfactory bulbUBERON:000226488.00gold quality
saliva-secreting glandUBERON:000104487.99gold quality
omental fat padUBERON:001041487.90gold quality
mouth mucosaUBERON:000372987.88gold quality
peritoneumUBERON:000235887.85gold quality
heartUBERON:000094887.82gold quality
midbrainUBERON:000189187.77gold quality
coronary arteryUBERON:000162187.76gold quality
small intestineUBERON:000210887.69gold quality
mucosa of stomachUBERON:000119987.66gold quality
fundus of stomachUBERON:000116087.53gold quality
embryoUBERON:000092287.33gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-MTAB-6524no142.43
E-ANND-3no0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Postcentral gyrustissue44.9
Skeletal muscletissue36.9medium
Hippocampustissue34.2low
Locus coeruleustissue32.7
Caudate putamentissue25.7
Nucleus accumbenstissue25.0
Frontal cortextissue24.8
Pancreastissue23.4medium
Pituitary glandtissue21.1
Choroid plexustissue21.0
Tonguetissue20.3
Salivary glandtissue18.5medium
Vaginatissue15.8medium
Testistissue15.0medium
Ovarytissue14.7low
Heart muscletissue13.4medium
Thyroid glandtissue13.2medium
Adrenal glandtissue12.7medium
Bone marrowtissue12.6medium
Parathyroid glandtissue12.5medium
Superior colliculitissue11.7
Duodenumtissue11.7medium
Cerebral cortextissue11.6medium
Thalamustissue11.6
Somatosensory cortextissue11.6
Cerebellumtissue11.5medium
Fallopian tubetissue11.5medium
Stomach 1tissue11.2medium
Small intestinetissue10.9medium
Midbraintissue10.8
Motor cortextissue10.7
Putamentissue10.7
Ponstissue10.5
Occipital cortextissue10.5
Placentatissue10.4medium
Hippocampal formationtissue10.4
Basal gangliatissue10.3medium
Olfactory bulbtissue10.3
Esophagustissue10.2medium
Skin 1tissue10.0medium
Prefrontal cortextissue10.0
Colontissue9.9medium
Medulla oblongatatissue9.9
Retrosplenial and cingulate cortextissue9.9
Lymph nodetissue9.8medium
Temporal cortextissue9.8
Spinal cordtissue9.6
Entorhinal cortextissue9.6
Insular cortextissue9.4
Prostatetissue9.3medium
Ventral forebraintissue9.3
Retrosplenial cortextissue9.3
Appendixtissue9.3medium
Substantia nigratissue9.1
Livertissue9.0medium
Kidneytissue9.0medium
Thymustissue9.0
Septumtissue9.0
Hypothalamustissue8.8
Gallbladdertissue8.6medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Precentral gyrus (47.1), Supplementary motor cortex (39.9), Postcentral gyrus, middle (39.6), Somatomor cortex, precentral gyrus (white matter) (37.9), Inferior parietal lobule (37.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MLST8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

25 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4692100.0067.322066
HSA-MIR-4673100.0066.641490
HSA-MIR-451499.9967.101870
HSA-MIR-4645-5P99.9865.811284
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-6764-5P99.7567.892304
HSA-MIR-556-3P99.7468.751203
HSA-MIR-149-3P99.7268.223963
HSA-MIR-6883-5P99.6968.053785
HSA-MIR-1915-3P99.5866.791988
HSA-MIR-1207-5P99.4969.112983
HSA-MIR-444199.4966.563216
HSA-MIR-4763-3P99.1067.832649
HSA-MIR-3190-5P98.8764.891345
HSA-MIR-6846-5P98.8165.861121
HSA-MIR-6848-5P98.8165.491126
HSA-MIR-423-5P98.6967.481522
HSA-MIR-3184-5P98.5667.131491
HSA-MIR-3944-5P98.5067.55997
HSA-MIR-211798.4867.971307
HSA-MIR-6773-3P98.1765.511213
HSA-MIR-4529-5P96.7465.77569
HSA-MIR-990096.0665.48557
HSA-MIR-4520-5P93.5465.23140

Functional genomics

gnomAD constraint: pLI 0.0205, LOEUF 0.679, missense Z 0.843 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000569417 — one region, missense o/e 0.93. DepMap (CRISPR cell-line fitness): dependent in 69.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SU-DHL-4 (-2.073), GAMG (-2.04), IGR-39 (-1.991), EWS502 (-1.876), KE-37 (-1.824), BT-549 (-1.806), LN-319 (-1.74), ONCO-DG-1 (-1.703), VM-CUB1 (-1.688), SNU-8 (-1.662), MFE-280 (-1.645), OUMS-23 (-1.574), NCI-H520 (-1.568), Saos-2 (-1.535), KARPAS-422 (-1.531).

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

OrganismSymbolGene ID
danio_reriomlst8ENSDARG00000003167
mus_musculusMlst8ENSMUSG00000024142
rattus_norvegicusMlst8ENSRNOG00000009667
drosophila_melanogasterLst8FBGN0264691
caenorhabditis_elegansmlst-8WBGENE00015697

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1929514) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)Records
abnormal heart development1
abnormal brain development1
abnormal telencephalon development1
internal hemorrhage1
decreased embryo size1
abnormal placenta morphology1
abnormal vitelline vasculature morphology1
embryonic growth retardation1
dilated vasculature1
embryonic lethality during organogenesis, complete penetrance1
thick placenta labyrinth1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Pongo abeliiQ5RAW899.9%Diamond
Bos taurusQ32PG399.7%Diamond
Xenopus tropicalisQ5I0B499.7%Diamond
Xenopus laevisQ6PA7299.7%Diamond
Gallus gallusQ5F3K497.9%Diamond
Macaca fascicularisQ4R2Z691.7%Diamond
Drosophila pseudoobscura pseudoobscuraQ29HG991.1%Diamond
Culex quinquefasciatusB0X2V984.9%Diamond
Arabidopsis thalianaF4IIK677.4%Diamond
Oryza sativa Japonica GroupQ9AYE477.0%Diamond
Schizosaccharomyces pombe 972h-O7418465.2%Diamond
Saccharomyces cerevisiae S288CP4131865.2%Diamond
Dictyostelium discoideumQ54D0863.6%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
MIR3180-5ncRNA100500916
RAB26protein-coding25837
SNORD60snoRNA26788
BRICD5protein-coding283870
CASKIN1protein-coding57524
TRAF7protein-coding84231
DNASE1L2protein-coding1775
E4F1protein-coding1877
PGPprotein-coding283871
SNHG19ncRNA100507303
ECI1-AS1ncRNA123706507
ECI1protein-coding1632

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): Q9BVC4, A0A0A0MR05, 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 IDNamesCanonical?
Q9BVC4-11yes
Q9BVC4-32
Q9BVC4-43
Q9BVC4-54

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

Domains & families (InterPro)

IDNameType
IPR001680WD40_rptRepeat
IPR011047Quinoprotein_ADH-like_sfHomologous_superfamily
IPR015943WD40/YVTN_repeat-like_dom_sfHomologous_superfamily
IPR019775WD40_repeat_CSConserved_site
IPR020472WD40_PAC1Repeat
IPR037588MLST8Family

Pfam: PF00400

UniProt features (79 total): strand 33, mutagenesis site 11, cross-link 8, repeat 7, splice variant 5, turn 5, modified residue 4, sequence conflict 3, chain 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

showing 30 of 45 structures by resolution:

PDBTitleMethodResolution (Å)
9T94cryo-EM structure of AKT phosphorylated mTOR complex 2, focused on a single protomerELECTRON MICROSCOPY2.6
9ZBKmTORC2 in complex with Akt1ELECTRON MICROSCOPY2.6
8ERARMC-5552 in complex with mTORC1 and FKBP12ELECTRON MICROSCOPY2.86
9T93cryo-EM structure of autophosphorylated mTOR complex 2, focused on a single protomerELECTRON MICROSCOPY2.86
6ZWOcryo-EM structure of human mTOR complex 2, focused on one halfELECTRON MICROSCOPY3
9T7Jcryo-EM structure of AKT phosphorylated mTOR complex 2, overall refinementELECTRON MICROSCOPY3
9TDTcryo-EM structure of dephosphorylated mTOR complex 2, focused on a single protomerELECTRON MICROSCOPY3
5WBYCrystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complexX-RAY DIFFRACTION3.1
9T92cryo-EM structure of autophosphorylated mTOR complex 2, overall refinementELECTRON MICROSCOPY3.1
9ED7Active state of mTOR on membraneELECTRON MICROSCOPY3.16
4JSNstructure of mTORdeltaN-mLST8 complexX-RAY DIFFRACTION3.2
6ZWMcryo-EM structure of human mTOR complex 2, overall refinementELECTRON MICROSCOPY3.2
7PE8cryo-EM structure of DEPTOR bound to human mTOR complex 2, focussed on one protomerELECTRON MICROSCOPY3.2
7UXCcryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex with symmetry expansionELECTRON MICROSCOPY3.2
7UXHcryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complexELECTRON MICROSCOPY3.2
9ZBJCryo-EM structure of human apo mTORC2ELECTRON MICROSCOPY3.2
6BCXmTORC1 structure refined to 3.0 angstromsELECTRON MICROSCOPY3.23
9ED4A composite map of mTORC1-Rag-Ragultor-4EBP1 on membraneELECTRON MICROSCOPY3.23
7TZOThe apo structure of human mTORC2 complexELECTRON MICROSCOPY3.28
4JSPstructure of mTORDeltaN-mLST8-ATPgammaS-Mg complexX-RAY DIFFRACTION3.3
9TDScryo-EM structure of dephosphorylated mTOR complex 2, overall refinementELECTRON MICROSCOPY3.3
8RCKCryoEM structure of mTORC1 with a paediatric kidney cancer-associated 1455-EWED-1458 …ELECTRON MICROSCOPY3.4
7PE7cryo-EM structure of DEPTOR bound to human mTOR complex 2, overall refinementELECTRON MICROSCOPY3.41
5WBUCrystal structure of mTOR(deltaN)-mLST8-PRAS40(alpha-helix & beta-strand) complexX-RAY DIFFRACTION3.42
4JT5mTORdeltaN-mLST8-pp242 complexX-RAY DIFFRACTION3.45
4JSVmTOR kinase structure, mechanism and regulation.X-RAY DIFFRACTION3.5
4JSXstructure of mTORDeltaN-mLST8-Torin2 complexX-RAY DIFFRACTION3.5
4JT6structure of mTORDeltaN-mLST8-PI-103 complexX-RAY DIFFRACTION3.6
9ED8Intermediate state of mTOR on membraneELECTRON MICROSCOPY3.61
7PEBcryo-EM structure of DEPTOR bound to human mTOR complex 1, focussed on one protomerELECTRON MICROSCOPY3.67

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BVC4-F192.150.82

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cell junctions; golgi apparatus

Antibody reliability (HPA): IH approved · IF approved

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)

TypePositions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo3)86, 215, 245, 261, 305
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)305, 313
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)313
N-acetylmethionine1, 1
Phosphoserine7
Phosphothreonine51

Mutagenesis-validated functional residues (11)

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

Function

Pathways and Gene Ontology

Reactome pathways

15 curated (TAS) of 41; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

41 pathways:

IDPathwayEvidence
R-HSA-5674400Constitutive Signaling by AKT1 E17K in Cancer ⚕curated
R-HSA-9920951Dengue virus modulates apoptosis ⚕curated
R-HSA-9639288Amino acids regulate mTORC1curated
R-HSA-389357CD28 dependent PI3K/Akt signalingcurated
R-HSA-380972Energy dependent regulation of mTOR by LKB1-AMPKcurated
R-HSA-3371571HSF1-dependent transactivationcurated
R-HSA-9856530High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cellscurated
R-HSA-165159MTOR signallingcurated
R-HSA-1632852Macroautophagycurated
R-HSA-1257604PIP3 activates AKT signalingcurated
R-HSA-8943724Regulation of PTEN gene transcriptioncurated
R-HSA-6804757Regulation of TP53 Degradationcurated
R-HSA-5628897TP53 Regulates Metabolic Genescurated
R-HSA-5218920VEGFR2 mediated vascular permeabilitycurated
R-HSA-166208mTORC1-mediated signallingcurated
R-HSA-1643685Disease ⚕—
R-HSA-5663202Diseases of signal transduction by growth factor receptors and second messengers ⚕—
R-HSA-2219528PI3K/AKT Signaling in Cancer ⚕—
R-HSA-1280218Adaptive Immune System—
R-HSA-9612973Autophagy—
R-HSA-3371556Cellular response to heat stress—
R-HSA-9711097Cellular response to starvation—
R-HSA-9855142Cellular responses to mechanical stimuli—
R-HSA-8953897Cellular responses to stimuli—
R-HSA-2262752Cellular responses to stress—
R-HSA-389356Co-stimulation by CD28—
R-HSA-74160Gene expression (Transcription)—
R-HSA-212436Generic Transcription Pathway—
R-HSA-168256Immune System—
R-HSA-9006925Intracellular signaling by second messengers—
R-HSA-6807070PTEN Regulation—
R-HSA-73857RNA Polymerase II Transcription—
R-HSA-388841Regulation of T cell activation by CD28 family—
R-HSA-5633007Regulation of TP53 Activity—
R-HSA-6806003Regulation of TP53 Expression and Degradation—
R-HSA-9860931Response of endothelial cells to shear stress—
R-HSA-162582Signal Transduction—
R-HSA-9006934Signaling by Receptor Tyrosine Kinases—
R-HSA-194138Signaling by VEGF—
R-HSA-3700989Transcriptional Regulation by TP53—
R-HSA-4420097VEGFA-VEGFR2 Pathway—

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 (16): DNA damage response (GO:0006974), cytoskeleton organization (GO:0007010), 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), 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)

GO Molecular Function (4): protein-macromolecule adaptor activity (GO:0030674), protein serine/threonine kinase activator activity (GO:0043539), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), TORC1 complex (GO:0031931), TORC2 complex (GO:0031932)

Reactome top-level categories

16 top-level categories:

CategoryPathways
MTOR signalling2
Intracellular signaling by second messengers1
Autophagy1
Signal Transduction1
Cellular response to heat stress1
Co-stimulation by CD281
VEGFA-VEGFR2 Pathway1
Transcriptional Regulation by TP531
PI3K/AKT Signaling in Cancer1
Regulation of TP53 Expression and Degradation1
PTEN Regulation1
Cellular response to starvation1
Response of endothelial cells to shear stress1
Dengue Virus-Host Interactions1
Immune System1
Signaling by Receptor Tyrosine Kinases1

GO top-level categories

51 GO namespaces:

CategoryTerms
TOR signaling3
cellular anatomical structure3
cellular response to stress2
TOR complex2
organelle organization1
autophagy1
negative regulation of catabolic process1
regulation of autophagy1
regulation of cell growth1
cell growth1
positive regulation of growth1
positive regulation of cellular process1
response to nutrient levels1
cellular response to stimulus1
intracellular signal transduction1
regulation of TOR signaling1
positive regulation of intracellular signal transduction1
actin cytoskeleton organization1
regulation of actin filament-based process1
regulation of cytoskeleton organization1
apoptotic process1
regulation of apoptotic process1
negative regulation of programmed cell death1
glycolytic process1
regulation of glycolytic process1
positive regulation of purine nucleotide catabolic process1
positive regulation of carbohydrate metabolic process1
positive regulation of ATP metabolic process1
lipid biosynthetic process1
positive regulation of biosynthetic process1
positive regulation of lipid metabolic process1
regulation of lipid biosynthetic process1
response to hypoxia1
cellular response to decreased oxygen levels1
response to osmotic stress1
cellular response to chemical stress1
cellular response to abiotic stimulus1
pentose-phosphate shunt1
regulation of pentose-phosphate shunt1
positive regulation of purine nucleotide metabolic process1
protein binding1
molecular adaptor activity1
protein serine/threonine kinase activity1
protein kinase activator activity1
protein kinase activity1
binding1
nuclear lumen1
intracellular anatomical structure1
lysosome1
lytic vacuole membrane1
cytoplasm1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO termNSEvidence
TORC1 signalingBPdirect assay
TORC2 signalingBPdirect assay
positive regulation of TOR signalingBPmutant phenotype
regulation of actin cytoskeleton organizationBPmutant phenotype
TORC1 complexCCdirect assay
TORC2 complexCCdirect assay
protein serine/threonine kinase activator activityMFdirect assay
protein-macromolecule adaptor activityMFdirect assay

Protein interactions and networks

STRING

showing 15 of 1,678 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
MLST8RPTORQ8N122992
MLST8RICTORQ6R327969
MLST8DEPTORQ8TB45922
MLST8MAPKAP1Q9BPZ7921
MLST8MTORP42345918
MLST8AKT1S1Q96B36893
MLST8SEC13P55735889
MLST8RPS6KB1P23443885
MLST8PRR5P85299858
MLST8RHEBQ15382851
MLST8EIF4EBP1Q13541848
MLST8FKBP1AP20071840
MLST8RPS6P08227793
MLST8TTI1O43156788
MLST8RRAGAQ7L523780

IntAct

Human interaction partners of MLST8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

PartnerInteraction typeMIscoreRecords
MTORphysical association0.8503
RPTORphysical association0.5602
CCT2association0.5301
APPL2physical association0.4902
NUDCphysical association0.4001
ATXN1physical association0.3702
E7physical association0.3702
A2Mphysical association0.3701
PRMT1physical association0.3701
TCP1association0.3501
ZNF609association0.3501
LCORphysical association0.0001
THADAphysical association0.0001
XPO4physical association0.0001
XPO6physical association0.0001

BioGRID (218 interactions; top human partners by supporting records): MTOR (Affinity Capture-Western; 33 records), RPTOR (Affinity Capture-Western; 17 records), RICTOR (Affinity Capture-Western; 15 records), CCT2 (Affinity Capture-MS; 5 records), KEAP1 (Affinity Capture-MS; 5 records), CCT7 (Affinity Capture-MS; 4 records), MAPKAP1 (Affinity Capture-Western; 4 records), CCT6B (Affinity Capture-MS; 3 records), FBXW7 (Affinity Capture-MS; 3 records), ACAT2 (Affinity Capture-MS; 2 records), CCT3 (Affinity Capture-MS; 2 records), CDK1 (Reconstituted Complex; 2 records), CLMP (Affinity Capture-MS; 2 records), ETV3 (Affinity Capture-MS; 2 records), FOXF2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

AEffectBMechanism
MLST8“form complex”mTORC1binding
MLST8“form complex”mTORC2binding

Protein complexes (CORUM) (13)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

13 complexes by size:

ComplexSubunitsMembers
★ mTORC1-TFEB-Rag-Ragulator complex11LAMTOR2, LAMTOR4, LAMTOR5, RPTOR, RRAGC, LAMTOR1, LAMTOR3, MLST8, MTOR, RRAGA, TFEB
★ DEPTOR-mTORC2 complex5DEPTOR, MLST8, MTOR, RPTOR, AKT1S1
★ DEPTOR-mTORC1 complex5AKT1S1, DEPTOR, MLST8, MTOR, RICTOR
★ mTORC1-TELO2-TTI1 complex5RPTOR, TELO2, TTI1, MLST8, MTOR
★ mTORC2-TELO2-TTI1 complex5RICTOR, TELO2, TTI1, MLST8, MTOR
★ mTORC1-RRAGB-RRAGC complex5MLST8, MTOR, RPTOR, RRAGB, RRAGC
★ mTORC1-RRAGB-RRAGD complex5RPTOR, RRAGB, RRAGD, MLST8, MTOR
★ mTORC2-PRR5 complex5PRR5, RICTOR, MAPKAP1, MLST8, MTOR
★ mTORC2-PRR5L complex5PRR5L, RICTOR, MAPKAP1, MLST8, MTOR
★ mTORC2 complex (MAPKAP1, MLST8, MTOR, RICTOR)4MAPKAP1, MLST8, MTOR, RICTOR
★ mTORC1-PRAS40 complex4AKT1S1, MLST8, MTOR, RPTOR
★ mTOR2 complex (MTOR, RICTOR, MLST8)3MTOR, RICTOR, MLST8
★ mTORC1 complex (MLST8, MTOR, RAPTOR)3RPTOR, MLST8, MTOR

Disease & clinical

Genetic variants

Variant evidence for MLST8: 48 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance36
Likely benign3
Benign0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 850):

Position(s)EffectΔscoreSites
16:2206660–2206661donor_loss1.00005
16:2207346–2207347donor_loss1.00006
16:2207350donor_loss1.00003
16:2208549donor_gain1.0000
16:2208614–2208615donor_loss1.00005
16:2205513–2205514donor_loss0.99004
16:2207111–2207112donor_loss0.99005
16:2207191–2207192acceptor_loss0.99006
16:2207321donor_gain0.9900
16:2208360donor_gain0.9900

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

CancerPrognosticp-value
Liver Hepatocellular Carcinoma (validation)unfavorable0.000305
Pancreatic Adenocarcinoma (validation)unfavorable0.000543
Liver Hepatocellular Carcinoma (TCGA)unfavorable0.00094

Disease associations

OMIM: gene MIM:612190 | disease phenotypes:

GWAS associations

1 associations:

StudyTraitp-value
GCST008163_267Height7e-7

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes MLST8 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

DrugTarget (ChEMBL)MembersMax phase
INDOXIMODmTORC132

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 277,263 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

13 molecules by phase:

MoleculeNamePhasePatents
CHEMBL1908360EVEROLIMUS474,649
CHEMBL413SIROLIMUS4174,652
CHEMBL1879463DACTOLISIB38,349
CHEMBL4084907BIMIRALISIB21,722
CHEMBL3586573CC-11521,300
CHEMBL1236962OMIPALISIB24,170
CHEMBL3586404ONATASERTIB21,138
CHEMBL3120215OSI-02721,950
CHEMBL3813842PAXALISIB21,149
CHEMBL3545097SAPANISERTIB22,649
CHEMBL2336325VISTUSERTIB22,054
CHEMBL1801204AZD-805513,479
CHEMBL5314926RMC-555212

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

134 measured of 179 human assays (182 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
CHEMBL5420034IC500.02 nM
CHEMBL5429186IC500.03 nM
CHEMBL5430111IC500.13 nM
CHEMBL5422529IC500.14 nM
CHEMBL5441038IC500.14 nM
CHEMBL5404497IC500.16 nM
RMC-5552IC500.17 nM
CHEMBL5419721IC500.19 nM
CHEMBL5399980IC500.19 nM
CHEMBL5430354IC500.22 nM
CHEMBL5413401IC500.23 nM
CHEMBL5408375IC500.24 nM
CHEMBL5422229IC500.24 nM
CHEMBL5404617IC500.26 nM
CHEMBL5427995IC500.27 nM
CHEMBL5440792IC500.28 nM
CHEMBL5394998IC500.29 nM
CHEMBL5219718KI0.3 nM
CHEMBL5419762IC500.37 nM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamineKI0.4 nMUS-11731973: Substituted pyrazolo[3,4-d]pyrimidines as mTOR inhibitors
CHEMBL5422165IC500.42 nM
CHEMBL5425648IC500.47 nM
CHEMBL5434290IC500.49 nM
CHEMBL5218590KI0.5 nM
CHEMBL5220536KI0.58 nM
CHEMBL5416606IC500.59 nM
CHEMBL5220152KI0.6 nM
CHEMBL5220948KI0.6 nM
CHEMBL5418134IC500.61 nM
CHEMBL5218916KI0.8 nM
3-(2-amino-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamineKI0.8 nMUS-11731973: Substituted pyrazolo[3,4-d]pyrimidines as mTOR inhibitors
CHEMBL4453693KD0.84 nM
CHEMBL5424277IC500.93 nM
SapanisertibIC501 nMUS-10172858: Combination pharmaceutical compositions and uses thereof
CHEMBL2338395IC501 nM
CHEMBL2338394IC501 nM
CHEMBL4563142IC501 nM
CHEMBL4445573KI1.9 nM
CHEMBL3813842IC502 nM
CHEMBL5218988KI2 nM
5-(2-aminobenzoxazol-5-yl)-7-methyl-7-methylsulfanylmethyl-6, 7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-4-ylamineKI2.4 nM
CHEMBL4758284KI2.7 nM
CHEMBL4749136KI3.4 nM
CHEMBL5218737KI3.9 nM
5-(7-methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amineIC504 nM
CHEMBL4754767KI4.4 nM
1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-oneIC506.3 nM
(S)-5-(4-morpholino-5a,6,8,9-tetrahydro-5H- pyrimido[5’,4’:4,5]pyrrolo[2,1-c][1,4]oxazin-2- yl)pyrimidin-2-amineKI8 nMUS-9556191: Aminoquinazoline derivatives and their salts and methods of use thereof
5-(2-aminobenzoxazol-5-yl)-7-isobutyl-6, 7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-4-ylamineKI12 nM
CHEMBL5420465IC5013 nM

ChEMBL bioactivities

385 potent at pChembl≥5 of 387 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.70IC500.02nMCHEMBL5420034
10.52IC500.03nMCHEMBL5429186
10.40IC500.04nMCHEMBL5418335
10.30IC500.05nMSIROLIMUS
10.30IC500.05nMEVEROLIMUS
10.22IC500.06nMSIROLIMUS
10.22IC500.06nMCHEMBL5420034
10.15IC500.07nMEVEROLIMUS
10.10IC500.08nMCHEMBL5429186
10.00IC500.1nMCHEMBL5218737
9.89IC500.13nMCHEMBL5430111
9.85IC500.14nMCHEMBL5422529
9.85IC500.14nMCHEMBL5441038
9.80IC500.16nMCHEMBL5404497
9.77IC500.17nMRMC-5552
9.74Ki0.18nMOMIPALISIB
9.74IC500.18nMOMIPALISIB
9.72IC500.19nMCHEMBL5419721
9.72IC500.19nMCHEMBL5399980
9.70IC500.2nMCHEMBL5219718
9.70IC500.2nMCHEMBL5218916
9.66IC500.22nMCHEMBL5430354
9.64IC500.23nMCHEMBL5413401
9.62IC500.24nMCHEMBL5408375
9.62IC500.24nMCHEMBL5422229
9.60EC500.25nMCHEMBL1765602
9.59IC500.26nMCHEMBL5404617
9.57IC500.27nMCHEMBL5427995
9.55IC500.28nMCHEMBL5440792
9.54IC500.29nMCHEMBL5394998
9.54IC500.29nMTORIN1
9.52Ki0.3nMOMIPALISIB
9.43IC500.37nMCHEMBL5419762
9.43IC500.37nMCHEMBL5431157
9.38IC500.42nMCHEMBL5422165
9.38IC500.42nMCHEMBL5419721
9.36IC500.44nMCHEMBL5430111
9.36IC500.44nMCHEMBL5441038
9.33IC500.47nMCHEMBL5425648
9.32IC500.48nMCHEMBL5422529
9.31IC500.49nMCHEMBL5434290
9.30IC500.5nMCHEMBL5218727
9.23IC500.59nMCHEMBL5416606
9.21IC500.61nMCHEMBL5418134
9.17IC500.67nMCHEMBL5404497
9.16IC500.69nMSAPANISERTIB
9.15IC500.7nMCHEMBL2334767
9.15IC500.7nMCHEMBL5218590
9.15IC500.7nMCHEMBL5220152
9.15IC500.7nMCHEMBL5413401

PubChem BioAssay actives

403 with measured affinity, of 757 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.

CompoundAssayTypeValueUnit
(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-tetrone1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic50<0.0001uM
(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-pentone1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic50<0.0001uM
(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-pentone1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic50<0.0001uM
(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-pentone1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
(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-pentone1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
(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-pentone1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
(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-pentone1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
(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-pentone1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
(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-pentone1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0001uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0001uM
(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-pentone1916680: Inhibition of mTORC1 in human Jurkat cells assessed as inhibition of S6K phosphorylation incubated for 4 hrs by Western blot analysisic500.0001uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0001uM
Sirolimus1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
Everolimus1916668: Inhibition of mTORC1 (unknown origin)ic500.0001uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(1-methylcyclobutyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-diamine1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assayic500.0002uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-(2,2-dimethylbutyl)pyrazolo[3,4-d]pyrimidine-4,6-diamine1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assayic500.0002uM
(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-pentone1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0002uM
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)-3-pyridinyl]benzenesulfonamide1871789: Inhibition of mTORC2 (unknown origin)ic500.0002uM
[(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)carbamate1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assayic500.0003uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0003uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0003uM
(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-pentone1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assayic500.0003uM
(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-pentone1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assayic500.0003uM
(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-pentone1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assayic500.0003uM
(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-pentone1916670: Inhibition of mTORC1 in human PC-3 cells assessed as measuring phosphorylated S6K level incubated for 24 hrs by AlphaLISA assayic500.0003uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0003uM
8-(6-methoxy-3-pyridinyl)-1-methyl-3-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]imidazo[4,5-c]quinolin-2-one1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0003uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one1994242: Inhibition of mTORC1 (unknown origin)ic500.0003uM
9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one1512676: Inhibition of mTORC1 in human HCT116 cells assessed as reduction in T389 phosphorylation on RPS6KB1 after 1 hr by Western blot analysisec500.0003uM
(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-tetrone1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0004uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0004uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0004uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0005uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamine1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assayic500.0005uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0005uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0006uM
[(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]carbamate1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0006uM
N-[5-[4,6-diamino-1-(2,2-dimethylbutyl)pyrazolo[3,4-d]pyrimidin-3-yl]-1,3-benzoxazol-2-yl]acetamide1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assayic500.0007uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-(2,2-dimethylpropyl)pyrazolo[3,4-d]pyrimidine-4,6-diamine1916693: Inhibition of mTORC1 in human A-431 cells assessed as phosphorylated S6RP level incubated for 3 hrs by HTRF assayic500.0007uM
Sapanisertib1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0007uM
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-dimethylpropanamide730846: Inhibition of mTORC1 in human NCI-PC3 cells assessed as inhibition of p70S6K phosphorylationic500.0007uM
[5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol1512672: Inhibition of mTORC1 (unknown origin)ic500.0008uM
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]propanamide1964503: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assayic500.0009uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
sodium arsenitedecreases expression, increases abundance, increases expression3
Valproic Aciddecreases expression, increases methylation2
aristolochic acid Idecreases expression1
TAK-243increases sumoylation1
bisphenol Adecreases expression1
trichostatin Aaffects expression1
beta-lapachoneincreases expression1
cobaltous chloridedecreases expression1
4-phenylenediaminedecreases expression1
sulphoraphenedecreases expression1
bisphenol Bincreases expression1
jinfukangincreases expression1
bisphenol AFincreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Temozolomideincreases expression1
Sunitinibincreases expression1
Air Pollutantsaffects expression, affects methylation, increases abundance1
Arsenicdecreases expression, increases abundance1
Benzo(a)pyreneaffects methylation1
Dimethyl Sulfoxideincreases expression1
Doxorubicindecreases expression1
Ivermectindecreases expression1
Seleniumincreases expression1
Smokedecreases expression1
Thiramdecreases expression1
Tobacco Smoke Pollutiondecreases expression1
Tretinoindecreases expression1
1-Methyl-4-phenylpyridiniumincreases expression1
Cadmium Chloridedecreases expression1
Copper Sulfatedecreases expression1

ChEMBL screening assays

275 unique, capped per target: 275 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1104625BindingInhibition of mTORC1 dependent P-S6K T389 phosphorylation in human U87MG cells after 6 hrs by immunoblotDiscovery 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):

CellosaurusNameCategorySex
CVCL_B1DUAbcam HCT 116 MLST8 KOCancer cell lineMale
CVCL_SY55HAP1 MLST8 (-)Cancer cell lineMale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MLST8 across ~30M SureChEMBL compounds — explore on Sugi Predict.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.