Details of the Drug Combination

General Information of Drug Combination (ID: DC24S20)

Drug Combination Name
MK-5108 10-hydroxycamptothecin
Indication
Disease Entry Status REF
Ovarian serous cystadenocarcinoma Investigative [1]
Component Drugs MK-5108   DMFGYKS 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: 3.63
Bliss Independence Score: 6.75
Loewe Additivity Score: 13.46
LHighest Single Agent (HSA) Score: 6.49

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-5108
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
MK-5108 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [4]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [4]
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Indication(s) of 10-hydroxycamptothecin
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [3]
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 [3]
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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 [5]
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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 [6]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Affects Response To Substance [7]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [6]
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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 DCX3LUQ ES2 Investigative [8]
Breast and ovarian cancer syndrome DCGRFMF UWB1289 Investigative [9]
Carcinoma DCK8NJU MDAMB436 Investigative [9]
Adenocarcinoma DCVHLJC NCIH23 Investigative [1]
Adenocarcinoma DCDSOC2 COLO320DM Investigative [1]
Adenocarcinoma DCJE7HQ DLD1 Investigative [1]
Germ cell tumour DCTU3AB PA1 Investigative [1]
Malignant melanoma DCNWGYJ RPMI7951 Investigative [1]
Mesothelioma DC87YTV MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DCHH7K5 A2780 Investigative [1]
Prostate carcinoma DCT62Z8 VCAP Investigative [1]
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⏷ Show the Full List of 11 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 (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
3 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.
4 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.
5 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
6 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.
7 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.
8 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.
9 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.