Details of the Drug Combination

General Information of Drug Combination (ID: DCN7UEV)

Drug Combination Name
ML323 Darunavir
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs ML323   DMY91A3 Darunavir   DMN3GCH
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 23.98
Bliss Independence Score: 23.98
Loewe Additivity Score: 34.78
LHighest Single Agent (HSA) Score: 34.78

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of ML323
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Preclinical [2]
ML323 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Deubiquitinating enzyme 1 (USP1) TTG9MT5 UBP1_HUMAN Inhibitor [5]
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Indication(s) of Darunavir
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [3]
Human immunodeficiency virus-1 infection 1C62 Phase 3 [4]
Darunavir Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human immunodeficiency virus Protease (HIV PR) TT5FNQT POL_HV1B1 Modulator [6]
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Darunavir Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [8]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [9]
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Darunavir Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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References

1 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.
2 Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov. 2018 Jan;17(1):57-78.
3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer. J Med Chem. 2014 Oct 9;57(19):8099-110.
6 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
7 Impact of drug transporters on cellular resistance towards saquinavir and darunavir. J Antimicrob Chemother. 2010 Nov;65(11):2319-28.
8 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
9 P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines. Biol Pharm Bull. 2009 Sep;32(9):1588-93.
10 Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41.