Details of the Drug Combination

General Information of Drug Combination (ID: DCLJ4W0)

• Drug Combination Name: Mefloquine + Enoxacin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mefloquine (DMWT905): Small molecular drug
  Enoxacin (DMYTE6L): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.48
  Bliss Independence Score: 2.48
  Loewe Additivity Score: 3.16
  LHighest Single Agent (HSA) Score: 3.21

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 Enoxacin

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[6]
Urinary tract infection	GC08	Approved	[7]

Enoxacin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Inhibitor	[11]

Enoxacin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[12]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[13]

Enoxacin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[14]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Affects Binding	[15]

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] Enoxacin FDA Label
• [7] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019616.
• [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] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [12] Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones. J Pharmacol Exp Ther. 2009 Feb;328(2):628-34.
• [13] Identification of influx transporter for the quinolone antibacterial agent levofloxacin. Mol Pharm. 2007 Jan-Feb;4(1):85-94.
• [14] Interaction study between enoxacin and fluvoxamine. Ther Drug Monit. 2005 Jun;27(3):349-53.
• [15] Computational and experimental studies on the inhibitory mechanism of hydroxychloroquine on hERG. Toxicology. 2021 Jun 30;458:152822. doi: 10.1016/j.tox.2021.152822. Epub 2021 May 28.