Details of the Drug Combination

General Information of Drug Combination (ID: DCGTJC1)

Drug Combination Name

Carboplatin MK-4827

Indication

Disease Entry	Status	REF
Solid Tumor, Adult	Phase 1	[1]

Component Drugs

Carboplatin DMG281S

MK-4827 DMLYGH4

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Carboplatin

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[2]
Carcinoma	2A00-2F9Z	Approved	[2]
Cholangiocarcinoma	2C12.10	Approved	[2]
Cutaneous melanoma	2C30	Approved	[2]
Epithelial ovarian cancer	2B5D	Approved	[2]
Fallopian tube neoplasm	N.A.	Approved	[2]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[2]
Lung adenocarcinoma	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[2]
Ovarian cancer	2C73	Approved	[3]
Ovarian disorder	N.A.	Approved	[2]
Ovarian neoplasm	N.A.	Approved	[2]
Ovarian serous cystadenocarcinoma	N.A.	Approved	[2]
Small-cell lung cancer	2C25.Y	Approved	[2]
Lung large cell carcinoma	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Carboplatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[6]
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Carboplatin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
High affinity copper uptake protein 1 (SLC31A1)	DTP8L4F	COPT1_HUMAN	Substrate	[7]
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Carboplatin Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[8]
Glutathione S-transferase theta-1 (GSTT1)	DE3PKUG	GSTT1_HUMAN	Metabolism	[8]
Metallothionein-1A (MT1A)	DE5ME8A	MT1A_HUMAN	Metabolism	[8]
Metallothionein-2A (MT2A)	DEFKGT7	MT2_HUMAN	Metabolism	[8]
Myeloperoxidase (MPO)	DEA3U9Y	PERM_HUMAN	Metabolism	[8]
Quinone reductase 1 (NQO1)	DENP5RY	NQO1_HUMAN	Metabolism	[8]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[8]
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⏷ Show the Full List of 7 DME(s)

Indication(s) of MK-4827

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 3	[4]
Breast cancer	2C60-2C65	Phase 2	[5]
Ewing sarcoma	2B52	Phase 1	[5]

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	[9]
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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	[10]
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Metabolism	[11]
Beta-glucuronidase (GUSB)	DEP54UE	BGLR_HUMAN	Metabolism	[11]
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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	[12]
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References

1	ClinicalTrials.gov (NCT03209401) Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies
2	Carboplatin FDA Label
3	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: 7624).
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	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6	Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
7	Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
8	PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
9	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
10	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.
11	Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
12	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.