Details of the Drug Combination

General Information of Drug Combination (ID: DC02439)

Drug Combination Name

MK-4827 Ridaforolimus

Indication

Disease Entry	Status	REF
Non small cell carcinoma	Investigative	[1]

Component Drugs

MK-4827 DMLYGH4

Ridaforolimus DMLHEU7

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: SKMES1

Zero Interaction Potency (ZIP) Score: 0.72

Bliss Independence Score: 1.65

Loewe Additivity Score: 2.03

LHighest Single Agent (HSA) Score: 3.91

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 Ridaforolimus

Disease Entry	ICD 11	Status	REF
Sarcoma	2A60-2C35	Phase 3	[4]

Ridaforolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_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	DCFE32M	ES2	Investigative	[10]
Breast and ovarian cancer syndrome	DCZDKU8	UWB1289	Investigative	[11]
Breast and ovarian cancer syndrome	DCPRVAD	UWB1289+BRCA1	Investigative	[11]
Breast carcinoma	DCDUHPX	ZR751	Investigative	[11]
Breast carcinoma	DCWNYY8	KPL1	Investigative	[11]
Breast carcinoma	DCD43IB	OCUBM	Investigative	[11]
Carcinoma	DCCLN9V	OV90	Investigative	[11]
Carcinoma	DCCLJF5	EFM192B	Investigative	[11]
Carcinoma	DCGQXQR	MDAMB436	Investigative	[11]
Colon carcinoma	DC4ZUBL	RKO	Investigative	[11]
Invasive ductal carcinoma	DC42T8R	T-47D	Investigative	[11]
Rectal adenocarcinoma	DCBPG0V	SW837	Investigative	[11]
Adenocarcinoma	DC64MA2	CAOV3	Investigative	[1]
Adenocarcinoma	DCNPSKT	OVCAR3	Investigative	[1]
Adenocarcinoma	DCFVPZL	NCIH1650	Investigative	[1]
Adenocarcinoma	DCI85EV	NCIH2122	Investigative	[1]
Adenocarcinoma	DCTKCSW	NCIH23	Investigative	[1]
Adenocarcinoma	DCW6IX0	COLO320DM	Investigative	[1]
Adenocarcinoma	DCZX6WL	DLD1	Investigative	[1]
Amelanotic melanoma	DCKF7RE	A2058	Investigative	[1]
Germ cell tumour	DCFFX4H	PA1	Investigative	[1]
Large cell lung carcinoma	DC05ILJ	NCI-H460	Investigative	[1]
Malignant melanoma	DCYI9EL	A375	Investigative	[1]
Malignant melanoma	DCHL0Z9	RPMI7951	Investigative	[1]
Malignant melanoma	DCSZLAH	SKMEL30	Investigative	[1]
Malignant melanoma	DCZ89NM	UACC62	Investigative	[1]
Mesothelioma	DCLTYOX	MSTO	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCXZMTP	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCXQHDR	SK-OV-3	Investigative	[1]
Prostate carcinoma	DCRW6IB	LNCAP	Investigative	[1]
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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 (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: 7884).
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	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.
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	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.