Details of the Drug Combination

General Information of Drug Combination (ID: DC1K916)

Drug Combination Name

MK-1775 MK-4827

Indication

Disease Entry	Status	REF
Malignant melanoma	Investigative	[1]

Component Drugs

MK-1775 DM3WDZ5

MK-4827 DMLYGH4

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: A375

Zero Interaction Potency (ZIP) Score: 12.48

Bliss Independence Score: 13.2

Loewe Additivity Score: 15.19

LHighest Single Agent (HSA) Score: 15.35

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of MK-1775

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

MK-1775 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_HUMAN	Inhibitor	[6]
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MK-1775 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Phosphorylation	[5]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[5]
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Indication(s) of MK-4827

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 3	[4]
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	[7]
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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	[8]
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Metabolism	[9]
Beta-glucuronidase (GUSB)	DEP54UE	BGLR_HUMAN	Metabolism	[9]
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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	[10]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCS4AFH	OVCAR3	Investigative	[1]
Adenocarcinoma	DCZJ0WT	A427	Investigative	[1]
Adenocarcinoma	DCUOZ58	NCIH2122	Investigative	[1]
Adenocarcinoma	DCUXGOA	NCIH23	Investigative	[1]
Adenocarcinoma	DCIAJFG	NCIH520	Investigative	[1]
Adenocarcinoma	DC1H17C	COLO320DM	Investigative	[1]
Adenocarcinoma	DCV06I1	HCT116	Investigative	[1]
Adenocarcinoma	DCQH4L2	HT29	Investigative	[1]
Adenocarcinoma	DCXKP27	SW-620	Investigative	[1]
Amelanotic melanoma	DCB756T	A2058	Investigative	[1]
Germ cell tumour	DC789LA	PA1	Investigative	[1]
Large cell lung carcinoma	DCOT6P6	NCI-H460	Investigative	[1]
Malignant melanoma	DCZ0GA3	RPMI7951	Investigative	[1]
Malignant melanoma	DCXL4GW	SKMEL30	Investigative	[1]
Non small cell carcinoma	DCSSQGR	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCEX7IO	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC8UK48	SK-OV-3	Investigative	[1]
Prostate carcinoma	DC94MO2	LNCAP	Investigative	[1]
Prostate carcinoma	DCP6R64	VCAP	Investigative	[1]
Breast carcinoma	DCMMN8B	ZR751	Investigative	[11]
Breast carcinoma	DCPCLUJ	KPL1	Investigative	[11]
Breast carcinoma	DCBUPX3	OCUBM	Investigative	[11]
Carcinoma	DC0IWEK	EFM192B	Investigative	[11]
Colon adenocarcinoma	DC6J8HT	LOVO	Investigative	[11]
Colon carcinoma	DC39R1W	RKO	Investigative	[11]
Invasive ductal carcinoma	DCB4CSV	T-47D	Investigative	[11]
Rectal adenocarcinoma	DC03UAA	SW837	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	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: 7702).
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	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.
5	Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
6	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.
7	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
8	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.
9	Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
10	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.
11	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.