Details of the Drug Combination

General Information of Drug Combination (ID: DCK7PJ9)

Drug Combination Name
MK-1775 GSK525762
Indication
Disease Entry Status REF
Breast and ovarian cancer syndrome Investigative [1]
Component Drugs MK-1775   DM3WDZ5 GSK525762   DMPAWBN
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: UWB1289+BRCA1
Zero Interaction Potency (ZIP) Score: 0.38
Bliss Independence Score: 12.28
Loewe Additivity Score: 10.89
LHighest Single Agent (HSA) Score: 12.18

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-1775
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
MK-1775 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Wee1-like protein kinase (WEE1) TTJFOAL WEE1_HUMAN Inhibitor [6]
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MK-1775 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [5]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [5]
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Indication(s) of GSK525762
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [3]
Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
GSK525762 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bromodomain-containing protein 4 (BRD4) TTRA6BO BRD4_HUMAN Modulator [8]
Bromodomain and extraterminal domain protein (BET) TTE4BSY NOUNIPROTAC Inhibitor [3]
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GSK525762 Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [9]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [10]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [10]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [10]
Protein-lysine 6-oxidase (LOX) OT1C2HIU LYOX_HUMAN Decreases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [11]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [11]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [7]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) OT25JBA3 F263_HUMAN Increases Expression [7]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [10]
Endothelial PAS domain-containing protein 1 (EPAS1) OTRE3O8U EPAS1_HUMAN Increases Expression [7]
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⏷ Show the Full List of 11 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCZ9JNY OVCAR3 Investigative [12]
Colon carcinoma DC4CW9F RKO Investigative [1]
Invasive ductal carcinoma DC6K20C T-47D Investigative [1]
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References

1 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
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: 7702).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 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: 7033).
5 Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
6 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
7 The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
8 Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
9 Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
10 An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
11 MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
12 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.