Details of the Drug Combination

General Information of Drug Combination (ID: DCTDB4W)

• Drug Combination Name: NAFTOPIDIL + Mefloquine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  NAFTOPIDIL (DMQ8R4E): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 2.187
  Bliss Independence Score: 3.002
  Loewe Additivity Score: 1.355
  LHighest Single Agent (HSA) Score: 2.211

Molecular Interaction Atlas of This Drug Combination

Indication(s) of NAFTOPIDIL

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[2]

NAFTOPIDIL Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Inhibitor	[7]

NAFTOPIDIL Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

NAFTOPIDIL Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[9]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Affects Expression	[9]

Indication(s) of Mefloquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[5]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[5]
Progressive multifocal leukoencephalopathy	8A45.02	Investigative	[6]

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	[10]

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	[11]

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	[12]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
• [4] 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.
• [5] Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
• [6] Mefloquine FDA Label
• [7] Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
• [8] Identification of human cytochrome P450 isozymes involved in the metabolism of naftopidil enantiomers in vitro. J Pharm Pharmacol. 2014 Nov;66(11):1534-51.
• [9] Autophagy Induced by Naftopidil Inhibits Apoptosis of Human Gastric Cancer Cells. Anticancer Res. 2018 Feb;38(2):803-809. doi: 10.21873/anticanres.12287.
• [10] An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
• [11] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [12] Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.