Details of the Drug Combination

General Information of Drug Combination (ID: DCS8SEX)

• Drug Combination Name: Darunavir + Anamorelin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Darunavir (DMN3GCH): Small molecular drug
  Anamorelin (DM6HXTS): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 12.65
  Bliss Independence Score: 12.65
  Loewe Additivity Score: 35.77
  LHighest Single Agent (HSA) Score: 35.77

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Darunavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[2]
Human immunodeficiency virus-1 infection	1C62	Phase 3	[3]

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	[5]

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	[6]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[8]

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	[9]

Indication(s) of Anamorelin

Disease Entry	ICD 11	Status	REF
Carbohydrate metabolism disorder	5C51.Z	Phase 3	[4]

Anamorelin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Growth hormone secretagogue receptor 1 (GHSR)	TTWDC17	GHSR_HUMAN	Stimulator	[10]
Alpha-glucosidase (GLA)	TTHCF4J	LYAG_HUMAN; GANAB_HUMAN; GANC_HUMAN	Modulator	[11]

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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT01395914) Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer-Cachexia (NSCLC-C): An Extension Study (ROMANA 3). U.S. National Institutes of Health.
• [5] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [6] Impact of drug transporters on cellular resistance towards saquinavir and darunavir. J Antimicrob Chemother. 2010 Nov;65(11):2319-28.
• [7] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [8] 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.
• [9] Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41.
• [10] Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers. Growth Horm IGF Res. 2009 Jun;19(3):267-73.
• [11] Absorption, elimination, and metabolism of CS-1036, a novel -amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption.Drug Metab Dispos.2013 Apr;41(4):878-87.