General Information of Drug Combination (ID: DCMT4I4)

Drug Combination Name
MK-4827 10-hydroxycamptothecin
Indication
Disease Entry Status REF
Ovarian serous cystadenocarcinoma Investigative [1]
Component Drugs MK-4827   DMLYGH4 10-hydroxycamptothecin   DM9WLN4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SK-OV-3
Zero Interaction Potency (ZIP) Score: 2.52
Bliss Independence Score: 4.93
Loewe Additivity Score: 7.25
LHighest Single Agent (HSA) Score: 6.97

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 10-hydroxycamptothecin
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
10-hydroxycamptothecin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [4]
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10-hydroxycamptothecin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [9]
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10-hydroxycamptothecin Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Response To Substance [10]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Affects Response To Substance [11]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [10]
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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 DC3QOO0 UWB1289+BRCA1 Investigative [12]
Breast carcinoma DCSAYP9 KPL1 Investigative [12]
Breast carcinoma DCL7X4H OCUBM Investigative [12]
Carcinoma DCSYC51 EFM192B Investigative [12]
Adenocarcinoma DCQEWFZ CAOV3 Investigative [1]
Adenocarcinoma DCZ9C5V OVCAR3 Investigative [1]
Adenocarcinoma DCGTHLV A427 Investigative [1]
Adenocarcinoma DCDYXZW NCIH2122 Investigative [1]
Adenocarcinoma DCFT0CP HT29 Investigative [1]
Amelanotic melanoma DCDVMON A2058 Investigative [1]
Germ cell tumour DCN7Q9T PA1 Investigative [1]
Malignant melanoma DCLCK79 HT144 Investigative [1]
Malignant melanoma DCYXQT0 UACC62 Investigative [1]
Malignant melanoma DCY0W6B RPMI7951 Investigative [1]
Mesothelioma DCB8GMJ MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DC36PMW A2780 Investigative [1]
Prostate carcinoma DC979RX VCAP Investigative [1]
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⏷ Show the Full List of 17 DrugCom(s)

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 Upregulation of p21WAF1/CIP1 in human breast cancer cell lines MCF-7 and MDA-MB-468 undergoing apoptosis induced by natural product anticancer drugs 10-hydroxycamptothecin and camptothecin through p53-dependent and independent pathways. Int J Oncol. 1998 Apr;12(4):793-804.
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 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
10 siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma cells to chemotherapeutic drugs. Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):450-6. doi: 10.1111/j.1440-1681.2007.04593.x.
11 Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11636-41. doi: 10.1073/pnas.1934692100. Epub 2003 Sep 16.
12 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.