MLST8
gene geneOn 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
| 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: 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
| Exon | Start | End |
|---|---|---|
| ENSE00002613104 | 2205454 | 2205512 |
| ENSE00003495720 | 2206031 | 2206214 |
| ENSE00003611614 | 2207035 | 2207110 |
| ENSE00003616825 | 2207193 | 2207345 |
| ENSE00003619428 | 2206358 | 2206409 |
| ENSE00003628750 | 2208210 | 2208334 |
| ENSE00003665527 | 2208450 | 2208613 |
| ENSE00003693495 | 2206497 | 2206659 |
| ENSE00004782172 | 2208759 | 2209453 |
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:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Muscle Skeletal | sqtl | 1.4e-99 | -1.01 | 16:2205221:C:T |
| Cells Cultured fibroblasts | eqtl | 8.9e-96 | +0.67 | 16:2205762:A:C |
| Thyroid | sqtl | 1.4e-78 | -0.91 | 16:2206046:AC:A |
| Cells Cultured fibroblasts | sqtl | 3.7e-72 | -1.01 | 16:2206325:C:T |
| Skin Sun Exposed Lower leg | sqtl | 1.2e-62 | -0.89 | 16:2206046:AC:A |
| Skin Not Sun Exposed Suprapubic | sqtl | 6.9e-60 | -0.91 | 16:2205221:C:T |
| Thyroid | eqtl | 2.0e-59 | +0.37 | 16:2206460:C:G |
| Testis | sqtl | 8.8e-52 | -1.06 | 16:2206046:AC:A |
| Esophagus Mucosa | sqtl | 5.3e-49 | -0.93 | 16:2206325:C:T |
| Nerve Tibial | sqtl | 7.1e-49 | -0.83 | 16:2206046:AC:A |
| Adipose Subcutaneous | sqtl | 2.3e-48 | -0.80 | 16:2205221:C:T |
| Cells EBV-transformed lymphocytes | sqtl | 6.0e-41 | -1.06 | 16:2206046:AC:A |
| Brain Cerebellum | sqtl | 1.3e-40 | -1.12 | 16:2207104:C:G |
| Brain Cerebellar Hemisphere | sqtl | 5.8e-39 | -1.06 | 16:2207104:C:G |
| Nerve Tibial | eqtl | 7.3e-39 | +0.31 | 16:2205221:C:T |
| Artery Tibial | eqtl | 1.2e-38 | +0.30 | 16:2206046:AC:A |
| Whole Blood | sqtl | 2.0e-38 | -0.73 | 16:2207104:C:G |
| Breast Mammary Tissue | sqtl | 2.8e-38 | -0.85 | 16:2206046:AC:A |
| Skin Sun Exposed Lower leg | eqtl | 6.4e-38 | +0.22 | 16:2205221:C:T |
| Skin Not Sun Exposed Suprapubic | eqtl | 2.7e-37 | +0.27 | 16:2205221:C:T |
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
showing 100 of 286 tissues 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 |
| left lobe of thyroid gland | UBERON:0001120 | 91.92 | gold quality |
| adenohypophysis | UBERON:0002196 | 91.60 | gold quality |
| adrenal cortex | UBERON:0001235 | 91.47 | gold quality |
| right uterine tube | UBERON:0001302 | 91.20 | gold quality |
| spinal cord | UBERON:0002240 | 91.14 | gold quality |
| body of stomach | UBERON:0001161 | 91.13 | gold quality |
| thyroid gland | UBERON:0002046 | 91.07 | gold quality |
| metanephros cortex | UBERON:0010533 | 91.02 | gold quality |
| telencephalon | UBERON:0001893 | 91.01 | gold quality |
| cerebral cortex | UBERON:0000956 | 90.99 | gold quality |
| brain | UBERON:0000955 | 90.95 | gold quality |
| testis | UBERON:0000473 | 90.94 | gold quality |
| ganglionic eminence | UBERON:0004023 | 90.84 | gold quality |
| forebrain | UBERON:0001890 | 90.81 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 90.80 | gold quality |
| stromal cell of endometrium | CL:0002255 | 90.73 | gold quality |
| right lobe of liver | UBERON:0001114 | 90.59 | gold quality |
| pituitary gland | UBERON:0000007 | 90.51 | gold quality |
| hypothalamus | UBERON:0001898 | 90.49 | gold quality |
| granulocyte | CL:0000094 | 90.37 | gold quality |
| skin of leg | UBERON:0001511 | 90.11 | gold quality |
| adrenal gland | UBERON:0002369 | 90.09 | gold quality |
| skin of abdomen | UBERON:0001416 | 89.88 | gold quality |
| right atrium auricular region | UBERON:0006631 | 89.87 | gold quality |
| left ovary | UBERON:0002119 | 89.81 | gold quality |
| ventricular zone | UBERON:0003053 | 89.78 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 89.69 | gold quality |
| transverse colon | UBERON:0001157 | 89.68 | gold quality |
| esophagus mucosa | UBERON:0002469 | 89.67 | gold quality |
| Ammon’s horn | UBERON:0001954 | 89.64 | gold quality |
| heart left ventricle | UBERON:0002084 | 89.63 | gold quality |
| right ovary | UBERON:0002118 | 89.53 | gold quality |
| minor salivary gland | UBERON:0001830 | 89.49 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 89.40 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 89.40 | gold quality |
| skeletal muscle organ | UBERON:0014892 | 89.20 | gold quality |
| muscle organ | UBERON:0001630 | 89.19 | gold quality |
| cardiac ventricle | UBERON:0002082 | 89.07 | gold quality |
| body of uterus | UBERON:0009853 | 89.07 | gold quality |
| esophagus | UBERON:0001043 | 89.06 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 88.95 | gold quality |
| cortical plate | UBERON:0005343 | 88.92 | gold quality |
| lower esophagus | UBERON:0013473 | 88.90 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 88.90 | gold quality |
| spleen | UBERON:0002106 | 88.64 | gold quality |
| stomach | UBERON:0000945 | 88.55 | gold quality |
| left uterine tube | UBERON:0001303 | 88.47 | gold quality |
| left coronary artery | UBERON:0001626 | 88.44 | gold quality |
| cardiac atrium | UBERON:0002081 | 88.42 | gold quality |
| substantia nigra | UBERON:0002038 | 88.41 | gold quality |
| gall bladder | UBERON:0002110 | 88.40 | gold quality |
| type B pancreatic cell | CL:0000169 | 88.37 | gold quality |
| temporal lobe | UBERON:0001871 | 88.32 | gold quality |
| ectocervix | UBERON:0012249 | 88.23 | gold quality |
| pancreas | UBERON:0001264 | 88.17 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 88.14 | gold quality |
| tibial nerve | UBERON:0001323 | 88.13 | gold quality |
| endocervix | UBERON:0000458 | 88.05 | gold quality |
| olfactory bulb | UBERON:0002264 | 88.00 | gold quality |
| saliva-secreting gland | UBERON:0001044 | 87.99 | gold quality |
| omental fat pad | UBERON:0010414 | 87.90 | gold quality |
| mouth mucosa | UBERON:0003729 | 87.88 | gold quality |
| peritoneum | UBERON:0002358 | 87.85 | gold quality |
| heart | UBERON:0000948 | 87.82 | gold quality |
| midbrain | UBERON:0001891 | 87.77 | gold quality |
| coronary artery | UBERON:0001621 | 87.76 | gold quality |
| small intestine | UBERON:0002108 | 87.69 | gold quality |
| mucosa of stomach | UBERON:0001199 | 87.66 | gold quality |
| fundus of stomach | UBERON:0001160 | 87.53 | gold quality |
| embryo | UBERON:0000922 | 87.33 | 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 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 80 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Postcentral gyrus | tissue | 44.9 | |
| Skeletal muscle | tissue | 36.9 | medium |
| Hippocampus | tissue | 34.2 | low |
| Locus coeruleus | tissue | 32.7 | |
| Caudate putamen | tissue | 25.7 | |
| Nucleus accumbens | tissue | 25.0 | |
| Frontal cortex | tissue | 24.8 | |
| Pancreas | tissue | 23.4 | medium |
| Pituitary gland | tissue | 21.1 | |
| Choroid plexus | tissue | 21.0 | |
| Tongue | tissue | 20.3 | |
| Salivary gland | tissue | 18.5 | medium |
| Vagina | tissue | 15.8 | medium |
| Testis | tissue | 15.0 | medium |
| Ovary | tissue | 14.7 | low |
| Heart muscle | tissue | 13.4 | medium |
| Thyroid gland | tissue | 13.2 | medium |
| Adrenal gland | tissue | 12.7 | medium |
| Bone marrow | tissue | 12.6 | medium |
| Parathyroid gland | tissue | 12.5 | medium |
| Superior colliculi | tissue | 11.7 | |
| Duodenum | tissue | 11.7 | medium |
| Cerebral cortex | tissue | 11.6 | medium |
| Thalamus | tissue | 11.6 | |
| Somatosensory cortex | tissue | 11.6 | |
| Cerebellum | tissue | 11.5 | medium |
| Fallopian tube | tissue | 11.5 | medium |
| Stomach 1 | tissue | 11.2 | medium |
| Small intestine | tissue | 10.9 | medium |
| Midbrain | tissue | 10.8 | |
| Motor cortex | tissue | 10.7 | |
| Putamen | tissue | 10.7 | |
| Pons | tissue | 10.5 | |
| Occipital cortex | tissue | 10.5 | |
| Placenta | tissue | 10.4 | medium |
| Hippocampal formation | tissue | 10.4 | |
| Basal ganglia | tissue | 10.3 | medium |
| Olfactory bulb | tissue | 10.3 | |
| Esophagus | tissue | 10.2 | medium |
| Skin 1 | tissue | 10.0 | medium |
| Prefrontal cortex | tissue | 10.0 | |
| Colon | tissue | 9.9 | medium |
| Medulla oblongata | tissue | 9.9 | |
| Retrosplenial and cingulate cortex | tissue | 9.9 | |
| Lymph node | tissue | 9.8 | medium |
| Temporal cortex | tissue | 9.8 | |
| Spinal cord | tissue | 9.6 | |
| Entorhinal cortex | tissue | 9.6 | |
| Insular cortex | tissue | 9.4 | |
| Prostate | tissue | 9.3 | medium |
| Ventral forebrain | tissue | 9.3 | |
| Retrosplenial cortex | tissue | 9.3 | |
| Appendix | tissue | 9.3 | medium |
| Substantia nigra | tissue | 9.1 | |
| Liver | tissue | 9.0 | medium |
| Kidney | tissue | 9.0 | medium |
| Thymus | tissue | 9.0 | |
| Septum | tissue | 9.0 | |
| Hypothalamus | tissue | 8.8 | |
| Gallbladder | tissue | 8.6 | medium |
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:
| 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
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
| 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 |
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 development | 1 |
| abnormal brain development | 1 |
| abnormal telencephalon development | 1 |
| internal hemorrhage | 1 |
| decreased embryo size | 1 |
| abnormal placenta morphology | 1 |
| abnormal vitelline vasculature morphology | 1 |
| embryonic growth retardation | 1 |
| dilated vasculature | 1 |
| embryonic lethality during organogenesis, complete penetrance | 1 |
| thick placenta labyrinth | 1 |
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.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Pongo abelii | Q5RAW8 | 99.9% | Diamond |
| Bos taurus | Q32PG3 | 99.7% | Diamond |
| Xenopus tropicalis | Q5I0B4 | 99.7% | Diamond |
| Xenopus laevis | Q6PA72 | 99.7% | Diamond |
| Gallus gallus | Q5F3K4 | 97.9% | Diamond |
| Macaca fascicularis | Q4R2Z6 | 91.7% | Diamond |
| Drosophila pseudoobscura pseudoobscura | Q29HG9 | 91.1% | Diamond |
| Culex quinquefasciatus | B0X2V9 | 84.9% | Diamond |
| Arabidopsis thaliana | F4IIK6 | 77.4% | Diamond |
| Oryza sativa Japonica Group | Q9AYE4 | 77.0% | Diamond |
| Schizosaccharomyces pombe 972h- | O74184 | 65.2% | Diamond |
| Saccharomyces cerevisiae S288C | P41318 | 65.2% | Diamond |
| Dictyostelium discoideum | Q54D08 | 63.6% | 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).
| Symbol | Type | Entrez |
|---|---|---|
| MIR3180-5 | ncRNA | 100500916 |
| RAB26 | protein-coding | 25837 |
| SNORD60 | snoRNA | 26788 |
| BRICD5 | protein-coding | 283870 |
| CASKIN1 | protein-coding | 57524 |
| TRAF7 | protein-coding | 84231 |
| DNASE1L2 | protein-coding | 1775 |
| E4F1 | protein-coding | 1877 |
| PGP | protein-coding | 283871 |
| SNHG19 | ncRNA | 100507303 |
| ECI1-AS1 | ncRNA | 123706507 |
| ECI1 | protein-coding | 1632 |
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 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 (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:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 9T94 | cryo-EM structure of AKT phosphorylated mTOR complex 2, focused on a single protomer | ELECTRON MICROSCOPY | 2.6 |
| 9ZBK | mTORC2 in complex with Akt1 | ELECTRON MICROSCOPY | 2.6 |
| 8ERA | RMC-5552 in complex with mTORC1 and FKBP12 | ELECTRON MICROSCOPY | 2.86 |
| 9T93 | cryo-EM structure of autophosphorylated mTOR complex 2, focused on a single protomer | ELECTRON MICROSCOPY | 2.86 |
| 6ZWO | cryo-EM structure of human mTOR complex 2, focused on one half | ELECTRON MICROSCOPY | 3 |
| 9T7J | cryo-EM structure of AKT phosphorylated mTOR complex 2, overall refinement | ELECTRON MICROSCOPY | 3 |
| 9TDT | cryo-EM structure of dephosphorylated mTOR complex 2, focused on a single protomer | ELECTRON MICROSCOPY | 3 |
| 5WBY | Crystal structure of mTOR(deltaN)-mLST8-PRAS40(beta-strand) complex | X-RAY DIFFRACTION | 3.1 |
| 9T92 | cryo-EM structure of autophosphorylated mTOR complex 2, overall refinement | ELECTRON MICROSCOPY | 3.1 |
| 9ED7 | Active state of mTOR on membrane | ELECTRON MICROSCOPY | 3.16 |
| 4JSN | structure of mTORdeltaN-mLST8 complex | X-RAY DIFFRACTION | 3.2 |
| 6ZWM | cryo-EM structure of human mTOR complex 2, overall refinement | ELECTRON MICROSCOPY | 3.2 |
| 7PE8 | cryo-EM structure of DEPTOR bound to human mTOR complex 2, focussed on one protomer | ELECTRON MICROSCOPY | 3.2 |
| 7UXC | cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex with symmetry expansion | ELECTRON MICROSCOPY | 3.2 |
| 7UXH | cryo-EM structure of the mTORC1-TFEB-Rag-Ragulator complex | ELECTRON MICROSCOPY | 3.2 |
| 9ZBJ | Cryo-EM structure of human apo mTORC2 | ELECTRON MICROSCOPY | 3.2 |
| 6BCX | mTORC1 structure refined to 3.0 angstroms | ELECTRON MICROSCOPY | 3.23 |
| 9ED4 | A composite map of mTORC1-Rag-Ragultor-4EBP1 on membrane | ELECTRON MICROSCOPY | 3.23 |
| 7TZO | The apo structure of human mTORC2 complex | ELECTRON MICROSCOPY | 3.28 |
| 4JSP | structure of mTORDeltaN-mLST8-ATPgammaS-Mg complex | X-RAY DIFFRACTION | 3.3 |
| 9TDS | cryo-EM structure of dephosphorylated mTOR complex 2, overall refinement | ELECTRON MICROSCOPY | 3.3 |
| 8RCK | CryoEM structure of mTORC1 with a paediatric kidney cancer-associated 1455-EWED-1458 … | ELECTRON MICROSCOPY | 3.4 |
| 7PE7 | cryo-EM structure of DEPTOR bound to human mTOR complex 2, overall refinement | ELECTRON MICROSCOPY | 3.41 |
| 5WBU | Crystal structure of mTOR(deltaN)-mLST8-PRAS40(alpha-helix & beta-strand) complex | X-RAY DIFFRACTION | 3.42 |
| 4JT5 | mTORdeltaN-mLST8-pp242 complex | X-RAY DIFFRACTION | 3.45 |
| 4JSV | mTOR kinase structure, mechanism and regulation. | X-RAY DIFFRACTION | 3.5 |
| 4JSX | structure of mTORDeltaN-mLST8-Torin2 complex | X-RAY DIFFRACTION | 3.5 |
| 4JT6 | structure of mTORDeltaN-mLST8-PI-103 complex | X-RAY DIFFRACTION | 3.6 |
| 9ED8 | Intermediate state of mTOR on membrane | ELECTRON MICROSCOPY | 3.61 |
| 7PEB | cryo-EM structure of DEPTOR bound to human mTOR complex 1, focussed on one protomer | ELECTRON MICROSCOPY | 3.67 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9BVC4-F1 | 92.15 | 0.82 |
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)
| Type | Positions |
|---|---|
| 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-acetylmethionine | 1, 1 |
| Phosphoserine | 7 |
| Phosphothreonine | 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
15 curated (TAS) of 41; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
41 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer ⚕ | curated |
| R-HSA-9920951 | Dengue virus modulates apoptosis ⚕ | curated |
| R-HSA-9639288 | Amino acids regulate mTORC1 | curated |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | curated |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | curated |
| R-HSA-3371571 | HSF1-dependent transactivation | curated |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells | curated |
| R-HSA-165159 | MTOR signalling | curated |
| R-HSA-1632852 | Macroautophagy | curated |
| R-HSA-1257604 | PIP3 activates AKT signaling | curated |
| R-HSA-8943724 | Regulation of PTEN gene transcription | curated |
| R-HSA-6804757 | Regulation of TP53 Degradation | curated |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | curated |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | curated |
| R-HSA-166208 | mTORC1-mediated signalling | curated |
| R-HSA-1643685 | Disease ⚕ | — |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers ⚕ | — |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer ⚕ | — |
| R-HSA-1280218 | Adaptive Immune System | — |
| R-HSA-9612973 | Autophagy | — |
| R-HSA-3371556 | Cellular response to heat stress | — |
| R-HSA-9711097 | Cellular response to starvation | — |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | — |
| R-HSA-8953897 | Cellular responses to stimuli | — |
| R-HSA-2262752 | Cellular responses to stress | — |
| R-HSA-389356 | Co-stimulation by CD28 | — |
| R-HSA-74160 | Gene expression (Transcription) | — |
| R-HSA-212436 | Generic Transcription Pathway | — |
| R-HSA-168256 | Immune System | — |
| R-HSA-9006925 | Intracellular signaling by second messengers | — |
| R-HSA-6807070 | PTEN Regulation | — |
| R-HSA-73857 | RNA Polymerase II Transcription | — |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | — |
| R-HSA-5633007 | Regulation of TP53 Activity | — |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | — |
| R-HSA-9860931 | Response of endothelial cells to shear stress | — |
| R-HSA-162582 | Signal Transduction | — |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | — |
| R-HSA-194138 | Signaling by VEGF | — |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | — |
| R-HSA-4420097 | VEGFA-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:
| 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 |
| Signaling by Receptor Tyrosine Kinases | 1 |
GO top-level categories
51 GO namespaces:
| Category | Terms |
|---|---|
| TOR signaling | 3 |
| cellular anatomical structure | 3 |
| cellular response to stress | 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 |
| response to nutrient levels | 1 |
| cellular response to stimulus | 1 |
| intracellular signal transduction | 1 |
| regulation of TOR signaling | 1 |
| positive regulation of intracellular signal transduction | 1 |
| 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 |
| cellular response to chemical stress | 1 |
| cellular response to abiotic stimulus | 1 |
| pentose-phosphate shunt | 1 |
| regulation of pentose-phosphate shunt | 1 |
| positive regulation of purine nucleotide metabolic process | 1 |
| protein binding | 1 |
| molecular adaptor activity | 1 |
| protein serine/threonine kinase activity | 1 |
| protein kinase activator activity | 1 |
| protein kinase activity | 1 |
| binding | 1 |
| nuclear lumen | 1 |
| intracellular anatomical structure | 1 |
| lysosome | 1 |
| lytic vacuole membrane | 1 |
| cytoplasm | 1 |
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 term | NS | Evidence |
|---|---|---|
| TORC1 signaling | BP | direct assay |
| TORC2 signaling | BP | direct assay |
| positive regulation of TOR signaling | BP | mutant phenotype |
| regulation of actin cytoskeleton organization | BP | mutant phenotype |
| TORC1 complex | CC | direct assay |
| TORC2 complex | CC | direct assay |
| protein serine/threonine kinase activator activity | MF | direct assay |
| protein-macromolecule adaptor activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 1,678 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| MLST8 | RPTOR | Q8N122 | 992 |
| MLST8 | RICTOR | Q6R327 | 969 |
| MLST8 | DEPTOR | Q8TB45 | 922 |
| MLST8 | MAPKAP1 | Q9BPZ7 | 921 |
| MLST8 | MTOR | P42345 | 918 |
| MLST8 | AKT1S1 | Q96B36 | 893 |
| MLST8 | SEC13 | P55735 | 889 |
| MLST8 | RPS6KB1 | P23443 | 885 |
| MLST8 | PRR5 | P85299 | 858 |
| MLST8 | RHEB | Q15382 | 851 |
| MLST8 | EIF4EBP1 | Q13541 | 848 |
| MLST8 | FKBP1A | P20071 | 840 |
| MLST8 | RPS6 | P08227 | 793 |
| MLST8 | TTI1 | O43156 | 788 |
| MLST8 | RRAGA | Q7L523 | 780 |
IntAct
Human interaction partners of MLST8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
15 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| MTOR | physical association | 0.850 | 3 |
| RPTOR | physical association | 0.560 | 2 |
| CCT2 | association | 0.530 | 1 |
| APPL2 | physical association | 0.490 | 2 |
| NUDC | physical association | 0.400 | 1 |
| ATXN1 | physical association | 0.370 | 2 |
| E7 | physical association | 0.370 | 2 |
| A2M | physical association | 0.370 | 1 |
| PRMT1 | physical association | 0.370 | 1 |
| TCP1 | association | 0.350 | 1 |
| ZNF609 | association | 0.350 | 1 |
| LCOR | physical association | 0.000 | 1 |
| THADA | physical association | 0.000 | 1 |
| XPO4 | physical association | 0.000 | 1 |
| XPO6 | physical association | 0.000 | 1 |
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:
| A | Effect | B | Mechanism |
|---|---|---|---|
| MLST8 | “form complex” | mTORC1 | binding |
| MLST8 | “form complex” | mTORC2 | binding |
Protein complexes (CORUM) (13)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
13 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| ★ mTORC1-TFEB-Rag-Ragulator complex | 11 | LAMTOR2, LAMTOR4, LAMTOR5, RPTOR, RRAGC, LAMTOR1, LAMTOR3, MLST8, MTOR, RRAGA, TFEB |
| ★ DEPTOR-mTORC2 complex | 5 | DEPTOR, MLST8, MTOR, RPTOR, AKT1S1 |
| ★ DEPTOR-mTORC1 complex | 5 | AKT1S1, DEPTOR, MLST8, MTOR, RICTOR |
| ★ mTORC1-TELO2-TTI1 complex | 5 | RPTOR, TELO2, TTI1, MLST8, MTOR |
| ★ mTORC2-TELO2-TTI1 complex | 5 | RICTOR, TELO2, TTI1, MLST8, MTOR |
| ★ mTORC1-RRAGB-RRAGC complex | 5 | MLST8, MTOR, RPTOR, RRAGB, RRAGC |
| ★ mTORC1-RRAGB-RRAGD complex | 5 | RPTOR, RRAGB, RRAGD, MLST8, MTOR |
| ★ mTORC2-PRR5 complex | 5 | PRR5, RICTOR, MAPKAP1, MLST8, MTOR |
| ★ mTORC2-PRR5L complex | 5 | PRR5L, RICTOR, MAPKAP1, MLST8, MTOR |
| ★ mTORC2 complex (MAPKAP1, MLST8, MTOR, RICTOR) | 4 | MAPKAP1, MLST8, MTOR, RICTOR |
| ★ mTORC1-PRAS40 complex | 4 | AKT1S1, MLST8, MTOR, RPTOR |
| ★ mTOR2 complex (MTOR, RICTOR, MLST8) | 3 | MTOR, RICTOR, MLST8 |
| ★ mTORC1 complex (MLST8, MTOR, RAPTOR) | 3 | RPTOR, 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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 36 |
| Likely benign | 3 |
| Benign | 0 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 850):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 16:2206660–2206661 | donor_loss | 1.0000 | 5 |
| 16:2207346–2207347 | donor_loss | 1.0000 | 6 |
| 16:2207350 | donor_loss | 1.0000 | 3 |
| 16:2208549 | donor_gain | 1.0000 | |
| 16:2208614–2208615 | donor_loss | 1.0000 | 5 |
| 16:2205513–2205514 | donor_loss | 0.9900 | 4 |
| 16:2207111–2207112 | donor_loss | 0.9900 | 5 |
| 16:2207191–2207192 | acceptor_loss | 0.9900 | 6 |
| 16:2207321 | donor_gain | 0.9900 | |
| 16:2208360 | donor_gain | 0.9900 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
3 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Liver Hepatocellular Carcinoma (validation) | unfavorable | 0.000305 |
| Pancreatic Adenocarcinoma (validation) | unfavorable | 0.000543 |
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 0.00094 |
Disease associations
OMIM: gene MIM:612190 | disease phenotypes:
GWAS associations
1 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST008163_267 | Height | 7e-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:
| Drug | Target (ChEMBL) | Members | Max phase |
|---|---|---|---|
| INDOXIMOD | mTORC1 | 3 | 2 |
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:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1908360 | EVEROLIMUS | 4 | 74,649 |
| CHEMBL413 | SIROLIMUS | 4 | 174,652 |
| CHEMBL1879463 | DACTOLISIB | 3 | 8,349 |
| CHEMBL4084907 | BIMIRALISIB | 2 | 1,722 |
| CHEMBL3586573 | CC-115 | 2 | 1,300 |
| CHEMBL1236962 | OMIPALISIB | 2 | 4,170 |
| CHEMBL3586404 | ONATASERTIB | 2 | 1,138 |
| CHEMBL3120215 | OSI-027 | 2 | 1,950 |
| CHEMBL3813842 | PAXALISIB | 2 | 1,149 |
| CHEMBL3545097 | SAPANISERTIB | 2 | 2,649 |
| CHEMBL2336325 | VISTUSERTIB | 2 | 2,054 |
| CHEMBL1801204 | AZD-8055 | 1 | 3,479 |
| CHEMBL5314926 | RMC-5552 | 1 | 2 |
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.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| CHEMBL5420034 | IC50 | 0.02 nM | |
| CHEMBL5429186 | IC50 | 0.03 nM | |
| CHEMBL5430111 | IC50 | 0.13 nM | |
| CHEMBL5422529 | IC50 | 0.14 nM | |
| CHEMBL5441038 | IC50 | 0.14 nM | |
| CHEMBL5404497 | IC50 | 0.16 nM | |
| RMC-5552 | IC50 | 0.17 nM | |
| CHEMBL5419721 | IC50 | 0.19 nM | |
| CHEMBL5399980 | IC50 | 0.19 nM | |
| CHEMBL5430354 | IC50 | 0.22 nM | |
| CHEMBL5413401 | IC50 | 0.23 nM | |
| CHEMBL5408375 | IC50 | 0.24 nM | |
| CHEMBL5422229 | IC50 | 0.24 nM | |
| CHEMBL5404617 | IC50 | 0.26 nM | |
| CHEMBL5427995 | IC50 | 0.27 nM | |
| CHEMBL5440792 | IC50 | 0.28 nM | |
| CHEMBL5394998 | IC50 | 0.29 nM | |
| CHEMBL5219718 | KI | 0.3 nM | |
| CHEMBL5419762 | IC50 | 0.37 nM | |
| 3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamine | KI | 0.4 nM | US-11731973: Substituted pyrazolo[3,4-d]pyrimidines as mTOR inhibitors |
| CHEMBL5422165 | IC50 | 0.42 nM | |
| CHEMBL5425648 | IC50 | 0.47 nM | |
| CHEMBL5434290 | IC50 | 0.49 nM | |
| CHEMBL5218590 | KI | 0.5 nM | |
| CHEMBL5220536 | KI | 0.58 nM | |
| CHEMBL5416606 | IC50 | 0.59 nM | |
| CHEMBL5220152 | KI | 0.6 nM | |
| CHEMBL5220948 | KI | 0.6 nM | |
| CHEMBL5418134 | IC50 | 0.61 nM | |
| CHEMBL5218916 | KI | 0.8 nM | |
| 3-(2-amino-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamine | KI | 0.8 nM | US-11731973: Substituted pyrazolo[3,4-d]pyrimidines as mTOR inhibitors |
| CHEMBL4453693 | KD | 0.84 nM | |
| CHEMBL5424277 | IC50 | 0.93 nM | |
| Sapanisertib | IC50 | 1 nM | US-10172858: Combination pharmaceutical compositions and uses thereof |
| CHEMBL2338395 | IC50 | 1 nM | |
| CHEMBL2338394 | IC50 | 1 nM | |
| CHEMBL4563142 | IC50 | 1 nM | |
| CHEMBL4445573 | KI | 1.9 nM | |
| CHEMBL3813842 | IC50 | 2 nM | |
| CHEMBL5218988 | KI | 2 nM | |
| 5-(2-aminobenzoxazol-5-yl)-7-methyl-7-methylsulfanylmethyl-6, 7-dihydro-5H-pyrrolo[3,2-d]pyrimidin-4-ylamine | KI | 2.4 nM | |
| CHEMBL4758284 | KI | 2.7 nM | |
| CHEMBL4749136 | KI | 3.4 nM | |
| CHEMBL5218737 | KI | 3.9 nM | |
| 5-(7-methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine | IC50 | 4 nM | |
| CHEMBL4754767 | KI | 4.4 nM | |
| 1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one | IC50 | 6.3 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-amine | KI | 8 nM | US-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-ylamine | KI | 12 nM | |
| CHEMBL5420465 | IC50 | 13 nM |
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
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.
| 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 | decreases expression, increases abundance, increases expression | 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 expression, affects methylation, increases abundance | 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)
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.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.