Details of the Drug Combination

General Information of Drug Combination (ID: DCPC4GY)

• Drug Combination Name: Mefloquine + Pargyline
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mefloquine (DMWT905): Small molecular drug
  Pargyline (DMM0HR1): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.98
  Bliss Independence Score: 0.98
  Loewe Additivity Score: 1.64
  LHighest Single Agent (HSA) Score: 1.69

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mefloquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[3]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[4]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[4]
Progressive multifocal leukoencephalopathy	8A45.02	Investigative	[5]

Mefloquine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium 80S ribosome (Malaria 80S)	TTT28H3	NOUNIPROTAC	Binder	[8]

Mefloquine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Mefloquine 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]

Indication(s) of Pargyline

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[6]
Muscular dystrophy	8C70	Patented	[7]
Skin imperfections	EK71	Patented	[7]

Pargyline Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Inhibitor	[7]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[11]

Pargyline Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Activity	[12]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Activity	[13]

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] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
• [3] ClinicalTrials.gov (NCT04347031) An Open Randomized Study of the Effectiveness of Mefloquine for the Treatment of Patients With COVID19. U.S. National Institutes of Health.
• [4] Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
• [5] Mefloquine FDA Label
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
• [8] An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
• [9] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [10] Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.
• [11] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [12] Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction. Chem Biol Interact. 2015 Mar 25;230:9-20.
• [13] Combining initro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. Chem Biol Interact. 2016 Jul 25;254:135-45.