Details of the Drug Combination

General Information of Drug Combination (ID: DCLAW1L)

Drug Combination Name
10-hydroxycamptothecin Topetecan
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs 10-hydroxycamptothecin   DM9WLN4 Topetecan   DMAE6LK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DU-145
Zero Interaction Potency (ZIP) Score: 4.24
Bliss Independence Score: 3.42
Loewe Additivity Score: 4.11
LHighest Single Agent (HSA) Score: 7.71

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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
Indication(s) of Topetecan
Disease Entry ICD 11 Status REF
Small-cell lung cancer 2C25.Y Approved [3]
Topetecan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [7]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCDSFJ0 MOLT-4 Investigative [8]
Anaplastic large cell lymphoma DCOY783 SR Investigative [8]
Childhood T acute lymphoblastic leukemia DCXW2S0 CCRF-CEM Investigative [8]
Clear cell renal cell carcinoma DCRP3VF 786-0 Investigative [8]
Glioma DCU4BT1 SF-539 Investigative [8]
Papillary renal cell carcinoma DCW0QG2 ACHN Investigative [8]
Renal cell carcinoma DC6GYJT SN12C Investigative [8]
Breast adenocarcinoma DCC8BXS MDA-MB-468 Investigative [9]
Adenocarcinoma DCQFK31 A549 Investigative [1]
Adenocarcinoma DCAQZW2 HCT116 Investigative [1]
Large cell lung carcinoma DC7E9BG NCI-H460 Investigative [1]
Lung adenocarcinoma DCNMWLQ HOP-62 Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 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 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 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020671.
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 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
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.