Details of the Drug Combination

General Information of Drug Combination (ID: DCH6XBJ)

• Drug Combination Name: LIDOFLAZINE + Lumefantrine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  LIDOFLAZINE (DMV23GL): Small molecular drug
  Lumefantrine (DM29GAD): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 4.426
  Bliss Independence Score: 4.483
  Loewe Additivity Score: 0.7
  LHighest Single Agent (HSA) Score: 6.058

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	[3]
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Inhibitor	[4]
Voltage-gated sodium channel alpha Nav1.3 (SCN3A)	TTAXZ0K	SCN3A_HUMAN	Inhibitor	[4]

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	[5]

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	[6]

Indication(s) of Lumefantrine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]

Lumefantrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium pump subunit alpha-1 (ATP1A1)	TTWK8D0	AT1A1_HUMAN	Binder	[7]

Lumefantrine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
DD2	DCP0K0L	DD2	Investigative	[9]

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] 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.
• [4] Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers. J Med Chem. 1994 Jan 21;37(2):268-74.
• [5] Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
• [6] 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.
• [7] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [8] Development of a paediatric physiologically based pharmacokinetic model to assess the impact of drug-drug interactions in tuberculosis co-infected malaria subjects: A case study with artemether-lumefantrine and the CYP3A4-inducer rifampicin. Eur J Pharm Sci. 2017 Aug 30;106:20-33.
• [9] 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.