Details of the Drug Combination

General Information of Drug Combination (ID: DCIHU9C)

• Drug Combination Name: Sotalol + Lumefantrine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Sotalol (DML60TN): Small molecular drug
  Lumefantrine (DM29GAD): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 4.752
  Bliss Independence Score: 5.837
  Loewe Additivity Score: 2.848
  LHighest Single Agent (HSA) Score: 3.593

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sotalol

Disease Entry	ICD 11	Status	REF
Sinus rhythm disorder	BC9Y	Approved	[2]

Sotalol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[4]

Sotalol Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[5]

Sotalol Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]

Sotalol Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[7]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Increases ADR	[7]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Increases ADR	[7]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases ADR	[7]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Increases ADR	[7]

Indication(s) of Lumefantrine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[3]

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	[8]

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	[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] 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: 7297).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25.
• [5] Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci. 2009 Jul;98(7):2529-39.
• [6] Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432.
• [7] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [8] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [9] 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.