General Information of Drug Combination (ID: DCCSGCB)

Drug Combination Name
SCH 727965 MK-5108
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs SCH 727965   DMCJLD1 MK-5108   DMFGYKS
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SW-620
Zero Interaction Potency (ZIP) Score: 9.54
Bliss Independence Score: 8.89
Loewe Additivity Score: 5.84
LHighest Single Agent (HSA) Score: 14.5

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 [4]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [4]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [4]
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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 [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [5]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [6]
Breast cancer type 2 susceptibility protein (BRCA2) OTF1XSV1 BRCA2_HUMAN Decreases Expression [6]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [6]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [6]
Cyclin-dependent kinase 12 (CDK12) OTZUDGNU CDK12_HUMAN Decreases Activity [6]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of MK-5108
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
MK-5108 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [7]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [7]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCHYKG3 HCT116 Investigative [8]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCCWBWD ES2 Investigative [8]
Invasive ductal carcinoma DC1J31K T-47D Investigative [9]
Adenocarcinoma DCPA2ZY CAOV3 Investigative [1]
Adenocarcinoma DCUW6N3 A427 Investigative [1]
Adenocarcinoma DCADS4G NCIH520 Investigative [1]
Adenocarcinoma DCZBWR7 COLO320DM Investigative [1]
Adenocarcinoma DCUODBQ DLD1 Investigative [1]
Adenocarcinoma DCCAV6I HT29 Investigative [1]
Germ cell tumour DCU98CA PA1 Investigative [1]
Malignant melanoma DCNSBDH A375 Investigative [1]
Malignant melanoma DCN7XPG RPMI7951 Investigative [1]
Malignant melanoma DCYT7CV SKMEL30 Investigative [1]
Malignant melanoma DCH18AH UACC62 Investigative [1]
Mesothelioma DCVW1WR MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DC6TFTC A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DC6VI1Z SK-OV-3 Investigative [1]
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⏷ Show the Full List of 17 DrugCom(s)

References

1 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.
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 ClinicalTrials.gov (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
4 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
5 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.
6 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.
7 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.
8 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.
9 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.