Details of the Drug Combination

General Information of Drug Combination (ID: DCDNUTT)

• Drug Combination Name: Verteporfin + Artemether
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  Verteporfin (DMIY6DB): Small molecular drug
  Artemether (DM48QOT): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 30.987
  Bliss Independence Score: 32.497
  Loewe Additivity Score: 4.273
  LHighest Single Agent (HSA) Score: 11.08

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Verteporfin

Disease Entry	ICD 11	Status	REF
Choroidal neovascularization	9B76	Approved	[2]
Exudative age-related macular degeneration	9B78.3Z	Approved	[2]
Psoriasis vulgaris	EA90	Approved	[3]

Verteporfin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[5]
ATP-binding cassette sub-family B member 6 (ABCB6)	DTF9Y2V	ABCB6_HUMAN	Substrate	[6]

Indication(s) of Artemether

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[4]

Artemether 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	[4]

Artemether Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[11]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

Artemether Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Affects Expression	[12]

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] Verteporfin FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [5] The tyrosine kinase inhibitor imatinib mesylate enhances the efficacy of photodynamic therapy by inhibiting ABCG2. Clin Cancer Res. 2007 Apr 15;13(8):2463-70.
• [6] Efficient purification and reconstitution of ATP binding cassette transporter B6 (ABCB6) for functional and structural studies. J Biol Chem. 2013 Aug 2;288(31):22658-69.
• [7] The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther. 1999 Oct;66(4):408-14.
• [8] The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects. Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):429-36.
• [9] Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017 Jul 3;16(1):267.
• [10] Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9.
• [11] Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
• [12] Fetal bovine serum and human constitutive androstane receptor: evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):221-30. doi: 10.1016/j.taap.2014.03.023. Epub 2014 Apr 12.