Details of the Drug Combination

General Information of Drug Combination (ID: DCUNSD2)

Drug Combination Name

MK-4827 SCH-900776

Indication

Disease Entry	Status	REF
Breast and ovarian cancer syndrome	Investigative	[1]

Component Drugs

MK-4827 DMLYGH4

SCH-900776 DM67EMK

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: UWB1289+BRCA1

Zero Interaction Potency (ZIP) Score: 5.51

Bliss Independence Score: 2.77

Loewe Additivity Score: 4.66

LHighest Single Agent (HSA) Score: 3.15

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
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DC386N8	ES2	Investigative	[10]
Breast carcinoma	DC8BAL5	KPL1	Investigative	[1]
Breast carcinoma	DC54IHN	OCUBM	Investigative	[1]
Carcinoma	DCU2Y1O	OV90	Investigative	[1]
Carcinoma	DCDZ94E	MDAMB436	Investigative	[1]
Colon carcinoma	DCU5P5B	RKO	Investigative	[1]
Rectal adenocarcinoma	DCQGSFQ	SW837	Investigative	[1]
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	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	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	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.
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.