Details of the Drug Combination

General Information of Drug Combination (ID: DC7USAS)

• Drug Combination Name: Artemether + BIX-01294
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Artemether (DM48QOT): Small molecular drug
  BIX-01294 (DM5CBNY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 7.478
  Bliss Independence Score: 1.319
  Loewe Additivity Score: 19.459
  LHighest Single Agent (HSA) Score: 1.562

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Artemether

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

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	[2]

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	[4]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[5]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[6]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[7]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[5]

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	[9]

Indication(s) of BIX-01294

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Preclinical	[3]

BIX-01294 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Euchromatic histone-lysine N-methyltransferase 1 (EHMT1)	TTOFXD7	EHMT1_HUMAN	Inhibitor	[10]
Histone-lysine N-methyltransferase EHMT2 (EHMT2)	TTS6RZT	EHMT2_HUMAN	Inhibitor	[10]

BIX-01294 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interferon alpha-2 (IFNA2)	OT4GII73	IFNA2_HUMAN	Increases Response To Substance	[11]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Increases Expression	[11]

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] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [3] Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286.
• [4] 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.
• [5] 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.
• [6] Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017 Jul 3;16(1):267.
• [7] 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.
• [8] Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
• [9] 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.
• [10] Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007 Feb 9;25(3):473-81.
• [11] Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment. PLoS One. 2014 Jul 31;9(7):e103915. doi: 10.1371/journal.pone.0103915. eCollection 2014.