Details of the Drug Combination

General Information of Drug Combination (ID: DCJZVFX)

• Drug Combination Name: ETHISTERONE + Darunavir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  ETHISTERONE (DMDXRP1): Small molecular drug
  Darunavir (DMN3GCH): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.17
  Bliss Independence Score: 1.17
  Loewe Additivity Score: 14.63
  LHighest Single Agent (HSA) Score: 14.63

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ETHISTERONE

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

ETHISTERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tyrosinase (TYR)	TTULVH8	TYRO_HUMAN	Inhibitor	[2]

ETHISTERONE Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase Sgk1 (SGK1)	OT301T1U	SGK1_HUMAN	Increases Expression	[5]
Myb-related protein A (MYBL1)	OTBJMC2P	MYBA_HUMAN	Increases Expression	[5]
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Increases Expression	[5]

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]

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]

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]

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] TOMOCOMD-CARDD descriptors-based virtual screening of tyrosinase inhibitors: evaluation of different classification model combinations using bond-b... Bioorg Med Chem. 2007 Feb 1;15(3):1483-503.
• [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] A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor in an MCF-7 Microarray Compendium. Chem Res Toxicol. 2021 Feb 15;34(2):313-329. doi: 10.1021/acs.chemrestox.0c00243. Epub 2021 Jan 6.
• [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.