General Information of Drug Combination (ID: DCQCSBE)

Drug Combination Name
SCH 727965 GSK525762
Indication
Disease Entry Status REF
Carcinoma Investigative [1]
Component Drugs SCH 727965   DMCJLD1 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: OV90
Zero Interaction Potency (ZIP) Score: 1.43
Bliss Independence Score: 5.22
Loewe Additivity Score: 4.83
LHighest Single Agent (HSA) Score: 4.9

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of SCH 727965
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Discontinued in Phase 3 [2]
SCH 727965 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [5]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [5]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [5]
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SCH 727965 Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [6]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [7]
Breast cancer type 2 susceptibility protein (BRCA2) OTF1XSV1 BRCA2_HUMAN Decreases Expression [7]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [7]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [7]
Cyclin-dependent kinase 12 (CDK12) OTZUDGNU CDK12_HUMAN Decreases Activity [7]
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⏷ Show the Full List of 7 DOT(s)
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 [9]
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 [10]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [11]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [11]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [11]
Protein-lysine 6-oxidase (LOX) OT1C2HIU LYOX_HUMAN Decreases Expression [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [12]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [12]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [8]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) OT25JBA3 F263_HUMAN Increases Expression [8]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [11]
Endothelial PAS domain-containing protein 1 (EPAS1) OTRE3O8U EPAS1_HUMAN Increases Expression [8]
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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
Breast and ovarian cancer syndrome DCCPGB4 UWB1289 Investigative [1]
Breast and ovarian cancer syndrome DC4ADUK UWB1289+BRCA1 Investigative [1]
Breast carcinoma DC5JBBF OCUBM Investigative [1]
Carcinoma DCD3N8V MDAMB436 Investigative [1]
Invasive ductal carcinoma DCRQZ86 T-47D Investigative [1]
Adenocarcinoma DC5DZDR NCIH2122 Investigative [13]
Amelanotic melanoma DC23MYV A2058 Investigative [13]
Malignant melanoma DCOO6US RPMI7951 Investigative [13]
Ovarian endometrioid adenocarcinoma DCR9QWK A2780 Investigative [13]
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⏷ Show the Full List of 9 DrugCom(s)

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: 7379).
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 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
6 Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.
7 CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077.
8 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.
9 Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
10 Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
11 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.
12 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.
13 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.