Details of the Drug Combination

General Information of Drug Combination (ID: DC8NQQO)

Drug Combination Name
10-hydroxycamptothecin SCH-900776
Indication
Disease Entry Status REF
Breast and ovarian cancer syndrome Investigative [1]
Component Drugs 10-hydroxycamptothecin   DM9WLN4 SCH-900776   DM67EMK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: UWB1289+BRCA1
Zero Interaction Potency (ZIP) Score: 4.74
Bliss Independence Score: 0.2
Loewe Additivity Score: 2.03
LHighest Single Agent (HSA) Score: 0.56

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of 10-hydroxycamptothecin
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
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 [2]
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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 [4]
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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 [5]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Affects Response To Substance [6]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [5]
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Indication(s) of SCH-900776
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [3]
SCH-900776 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [7]
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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 DCHRE1S UWB1289 Investigative [1]
Adenocarcinoma DCSTISN CAOV3 Investigative [8]
Adenocarcinoma DCNHJHZ OVCAR3 Investigative [8]
Adenocarcinoma DCQGMIV NCIH2122 Investigative [8]
Adenocarcinoma DC91IWK COLO320DM Investigative [8]
Adenocarcinoma DCJMOTP HT29 Investigative [8]
Amelanotic melanoma DCF6ISV A2058 Investigative [8]
Germ cell tumour DCKZVU9 PA1 Investigative [8]
Malignant melanoma DCLL2UG A375 Investigative [8]
Malignant melanoma DCY86O0 RPMI7951 Investigative [8]
Mesothelioma DCN4BHW MSTO Investigative [8]
Ovarian serous cystadenocarcinoma DCUDNPU SK-OV-3 Investigative [8]
Prostate carcinoma DCF1JOZ VCAP Investigative [8]
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⏷ Show the Full List of 13 DrugCom(s)

References

1 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.
2 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.
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: 7943).
4 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
5 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.
6 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.
7 Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
8 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.