Details of the Drug Combination

General Information of Drug Combination (ID: DCW3BOR)

• Drug Combination Name: Lacosamide + Mefloquine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Lacosamide (DMVM6QR): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.11
  Bliss Independence Score: 3.11
  Loewe Additivity Score: 4.11
  LHighest Single Agent (HSA) Score: 4.15

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lacosamide

Disease Entry	ICD 11	Status	REF
Convulsion	8A68.Z	Approved	[2]
Epilepsy	8A60-8A68	Approved	[3]
Diabetic neuropathy	8C0Z	Phase 3	[2]

Lacosamide Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated sodium channel alpha Nav1.9 (SCN11A)	TTN9VTF	SCNBA_HUMAN	Inhibitor	[3]
Voltage-gated sodium channel (Nav)	TTIG65Q	NOUNIPROTAC	Inhibitor	[3]
Dihydropyrimidinase related protein 2 (DPYSL2)	TTZCW3T	DPYL2_HUMAN	Modulator	[8]

Lacosamide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[9]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[10]

Indication(s) of Mefloquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[6]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[6]
Progressive multifocal leukoencephalopathy	8A45.02	Investigative	[7]

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]

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] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7472).
• [3] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [4] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
• [5] 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.
• [6] Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
• [7] Mefloquine FDA Label
• [8] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [9] Lacosamide: what can be expected from the next new antiepileptic drug? Epilepsy Curr. 2009 Sep-Oct;9(5):133-4.
• [10] Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013 Dec;35(6):849-52.
• [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.