Details of the Drug Combination

General Information of Drug Combination (ID: DCTSC9P)

Drug Combination Name
Idarubicin 10-hydroxycamptothecin
Indication
Disease Entry Status REF
Malignant melanoma Investigative [1]
Component Drugs Idarubicin   DMM0XGL 10-hydroxycamptothecin   DM9WLN4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: RPMI7951
Zero Interaction Potency (ZIP) Score: 0.32
Bliss Independence Score: 2.64
Loewe Additivity Score: 3.62
LHighest Single Agent (HSA) Score: 6.19

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Idarubicin
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [2]
Acute myeloid leukaemia 2A60 Approved [3]
Adult acute monocytic leukemia N.A. Approved [2]
Childhood acute megakaryoblastic leukemia N.A. Approved [2]
Leukemia N.A. Approved [2]
Idarubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [6]
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Idarubicin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
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Idarubicin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [9]
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Idarubicin Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [10]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [5]
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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 [7]
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10-hydroxycamptothecin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [11]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Anaplastic large cell lymphoma DCEIS06 SR Investigative [12]
Adenocarcinoma DCTDZRI OVCAR3 Investigative [1]
Adenocarcinoma DCJYYQA NCIH2122 Investigative [1]
Amelanotic melanoma DCPSQTW A2058 Investigative [1]
Ovarian endometrioid adenocarcinoma DC3FGF0 A2780 Investigative [1]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
2 Idarubicin 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: 7083).
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 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
9 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
10 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
11 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.
12 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966