Details of the Drug Combination

General Information of Drug Combination (ID: DC89FCR)

• Drug Combination Name: LIDOFLAZINE + Mefloquine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  LIDOFLAZINE (DMV23GL): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 1.871
  Bliss Independence Score: 2.628
  Loewe Additivity Score: 1.435
  LHighest Single Agent (HSA) Score: 5.1

Molecular Interaction Atlas of This Drug Combination

Indication(s) of LIDOFLAZINE

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[2]

LIDOFLAZINE Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Solute carrier family 29 member 1 (SLC29A1)	TTLXAKE	S29A1_HUMAN	Inhibitor	[7]
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Inhibitor	[8]
Voltage-gated sodium channel alpha Nav1.3 (SCN3A)	TTAXZ0K	SCN3A_HUMAN	Inhibitor	[8]

LIDOFLAZINE 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]

LIDOFLAZINE Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[10]

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	[11]

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	[12]

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	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
DD2	DC7RHOA	DD2	Investigative	[14]

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] Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibit... J Med Chem. 2007 Aug 9;50(16):3906-20.
• [8] Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers. J Med Chem. 1994 Jan 21;37(2):268-74.
• [9] Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
• [10] Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther. 2006 Mar;316(3):1098-106. doi: 10.1124/jpet.105.093393. Epub 2005 Nov 8.
• [11] An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
• [12] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [13] Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.
• [14] 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.