Details of the Drug Combination

General Information of Drug Combination (ID: DCO6RGX)

Drug Combination Name
GSK690693 Cotellic
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs GSK690693   DMRBVHE Cotellic   DMF9M57
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: RD
Zero Interaction Potency (ZIP) Score: 9.303
Bliss Independence Score: 10.769
Loewe Additivity Score: 6.866
LHighest Single Agent (HSA) Score: 8.154

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GSK690693
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [2]
GSK690693 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RAC-gamma serine/threonine-protein kinase (AKT3) TTAZ05C AKT3_HUMAN Modulator [6]
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GSK690693 Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Decreases Phosphorylation [7]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Response To Substance [8]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Tuberin (TSC2) OT47LWI9 TSC2_HUMAN Decreases Phosphorylation [9]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Phosphorylation [10]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [9]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [7]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Cotellic
Disease Entry ICD 11 Status REF
Melanoma 2C30 Phase 3 [3]
Breast cancer 2C60-2C65 Phase 2 [4]
Head and neck cancer 2D42 Phase 1 [4]
Renal cell carcinoma 2C90 Phase 1 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
Urothelial carcinoma 2C92.0 Phase 1 [4]

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DC7VE8K Rh36 Investigative [1]
Embryonal rhabdomyosarcoma DCRSWNG CTR Investigative [1]
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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 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: 5196).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT01106599) A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
6 Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.Cancer Res.2008 Apr 1;68(7):2366-74.
7 Xanthohumol inhibits non-small cell lung cancer by activating PUMA-mediated apoptosis. Toxicology. 2022 Mar 30;470:153141. doi: 10.1016/j.tox.2022.153141. Epub 2022 Mar 5.
8 PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
9 Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells. Mol Cancer Ther. 2012 Jul;11(7):1510-7. doi: 10.1158/1535-7163.MCT-11-0907. Epub 2012 Apr 24.
10 Combined SRPK and AKT pharmacological inhibition is synergistic in T-cell acute lymphoblastic leukemia cells. Toxicol In Vitro. 2020 Jun;65:104777. doi: 10.1016/j.tiv.2020.104777. Epub 2020 Jan 18.