General Information of Drug Combination (ID: DC386N8)

Drug Combination Name
MK-4827 SCH-900776
Indication
Disease Entry Status REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour Investigative [1]
Component Drugs MK-4827   DMLYGH4 SCH-900776   DM67EMK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: ES2
Zero Interaction Potency (ZIP) Score: 13.15
Bliss Independence Score: 12.57
Loewe Additivity Score: 14.05
LHighest Single Agent (HSA) Score: 14.73

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [2]
Breast cancer 2C60-2C65 Phase 2 [3]
Ewing sarcoma 2B52 Phase 1 [3]
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 [5]
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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 [6]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [7]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [7]
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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 [8]
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Indication(s) of SCH-900776
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [4]
SCH-900776 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [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 DCUNSD2 UWB1289+BRCA1 Investigative [10]
Breast carcinoma DC8BAL5 KPL1 Investigative [10]
Breast carcinoma DC54IHN OCUBM Investigative [10]
Carcinoma DCU2Y1O OV90 Investigative [10]
Carcinoma DCDZ94E MDAMB436 Investigative [10]
Colon carcinoma DCU5P5B RKO Investigative [10]
Rectal adenocarcinoma DCQGSFQ SW837 Investigative [10]
Adenocarcinoma DCJCNIO CAOV3 Investigative [11]
Adenocarcinoma DC2ECJ4 OVCAR3 Investigative [11]
Adenocarcinoma DCTHA6M A427 Investigative [11]
Adenocarcinoma DC4K3HZ NCIH2122 Investigative [11]
Adenocarcinoma DCIFKNW NCIH23 Investigative [11]
Adenocarcinoma DCLTPD7 COLO320DM Investigative [11]
Adenocarcinoma DC8OA8H DLD1 Investigative [11]
Adenocarcinoma DCCTRVY HT29 Investigative [11]
Amelanotic melanoma DCYKMNN A2058 Investigative [11]
Germ cell tumour DC1TZ3T PA1 Investigative [11]
Large cell lung carcinoma DCB1LP2 NCI-H460 Investigative [11]
Malignant melanoma DC1DY7H A375 Investigative [11]
Malignant melanoma DC6MF7R HT144 Investigative [11]
Malignant melanoma DCL5VYC RPMI7951 Investigative [11]
Malignant melanoma DCC65TQ SKMEL30 Investigative [11]
Malignant melanoma DCPFW2S UACC62 Investigative [11]
Mesothelioma DC5NJSB MSTO Investigative [11]
Non small cell carcinoma DCFLMGE SKMES1 Investigative [11]
Ovarian endometrioid adenocarcinoma DC23HDQ A2780 Investigative [11]
Ovarian serous cystadenocarcinoma DCPYSTM SK-OV-3 Investigative [11]
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⏷ Show the Full List of 27 DrugCom(s)

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 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.
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: 7943).
5 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
6 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.
7 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
8 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.
9 Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
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.
11 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.