General Information of Drug Combination (ID: DCE21DR)

Drug Combination Name
MK-5108 MK-4827
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs MK-5108   DMFGYKS MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HCT116
Zero Interaction Potency (ZIP) Score: 3.34
Bliss Independence Score: 1.85
Loewe Additivity Score: 2.29
LHighest Single Agent (HSA) Score: 2.17

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-5108
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
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 [5]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
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Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [3]
Breast cancer 2C60-2C65 Phase 2 [4]
Ewing sarcoma 2B52 Phase 1 [4]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [6]
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MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [7]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [8]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [8]
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MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [9]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DCBGGSO UWB1289+BRCA1 Investigative [10]
Breast carcinoma DC22EC6 KPL1 Investigative [10]
Breast carcinoma DCOJGWP OCUBM Investigative [10]
Carcinoma DCSQ5YL EFM192B Investigative [10]
Colon carcinoma DCLKJ8Q RKO Investigative [10]
Invasive ductal carcinoma DCDIC8Q T-47D Investigative [10]
Rectal adenocarcinoma DC30C6P SW837 Investigative [10]
Adenocarcinoma DC5W0QB CAOV3 Investigative [1]
Adenocarcinoma DCPONMC OVCAR3 Investigative [1]
Adenocarcinoma DCR8G24 A427 Investigative [1]
Adenocarcinoma DCO2W8T NCIH2122 Investigative [1]
Adenocarcinoma DCNYE0W NCIH520 Investigative [1]
Adenocarcinoma DCOTPP6 COLO320DM Investigative [1]
Adenocarcinoma DCGZ7WH DLD1 Investigative [1]
Adenocarcinoma DCT21UE HT29 Investigative [1]
Adenocarcinoma DCC3F5K SW-620 Investigative [1]
Amelanotic melanoma DC0XA7R A2058 Investigative [1]
Malignant melanoma DCQO4VA A375 Investigative [1]
Malignant melanoma DC2QYN9 RPMI7951 Investigative [1]
Malignant melanoma DCND5UR SKMEL30 Investigative [1]
Mesothelioma DCXDZ90 MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DCTRTM1 A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DCKW65Q SK-OV-3 Investigative [1]
Prostate carcinoma DCFEYQ1 VCAP Investigative [1]
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⏷ Show the Full List of 24 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 ClinicalTrials.gov (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
3 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 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.
6 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
7 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
8 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
9 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
10 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.