Details of the Drug Combination

General Information of Drug Combination (ID: DCAVKY1)

Drug Combination Name
torin 1 ZSTK474
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs torin 1   DMZD0NA ZSTK474   DMVIMQX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 0.407
Bliss Independence Score: 3.676
Loewe Additivity Score: 5.801
LHighest Single Agent (HSA) Score: 5.801

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of torin 1
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
torin 1 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [5]
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torin 1 Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [6]
Polyadenylate-binding protein 1 (PABPC1) OT54LG0P PABP1_HUMAN Decreases Expression [7]
Elongation factor 2 (EEF2) OTZ7SZ39 EF2_HUMAN Increases Phosphorylation [7]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [8]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [9]
Small ribosomal subunit protein uS10 (RPS20) OTI8052R RS20_HUMAN Decreases Expression [7]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Expression [7]
Large ribosomal subunit protein eL32 (RPL32) OTKRQJT4 RL32_HUMAN Decreases Expression [7]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [7]
La-related protein 1 (LARP1) OT5HPUOA LARP1_HUMAN Increases Response To Substance [7]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of ZSTK474
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
ZSTK474 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [10]
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ZSTK474 Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) OTOMP6TH PK3CD_HUMAN Decreases Activity [11]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [11]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Activity [11]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) OTO8JQJA PK3CB_HUMAN Decreases Activity [11]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [12]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009 Mar 20;284(12):8023-32.
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7965).
4 Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation. Autophagy. 2016 Nov;12(11):2085-2097. doi: 10.1080/15548627.2016.1226733. Epub 2016 Sep 14.
5 Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer. J Med Chem. 2010 Oct 14;53(19):7146-55.
6 A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and diabetes. Nat Commun. 2018 Apr 12;9(1):1438. doi: 10.1038/s41467-018-03939-w.
7 La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). J Biol Chem. 2015 Jun 26;290(26):15996-6020. doi: 10.1074/jbc.M114.621730. Epub 2015 May 4.
8 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
9 Inhibition of autophagy potentiates the antitumor effect of the multikinase inhibitor sorafenib in hepatocellular carcinoma. Int J Cancer. 2012 Aug 1;131(3):548-57. doi: 10.1002/ijc.26374. Epub 2011 Sep 12.
10 Combination of the PI3K inhibitor ZSTK474 with a PSMA-targeted immunotoxin accelerates apoptosis and regression of prostate cancer. Neoplasia. 2013 Oct;15(10):1172-83.
11 Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474). J Med Chem. 2011 Oct 27;54(20):7105-26. doi: 10.1021/jm200688y. Epub 2011 Sep 27.
12 The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomas. Mol Cancer Ther. 2013 Oct;12(10):1994-2005. doi: 10.1158/1535-7163.MCT-13-0206. Epub 2013 Jul 19.