Details of the Drug Combination

General Information of Drug Combination (ID: DCKD960)

• Drug Combination Name: Fomepizole + Atovaquone
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Fomepizole (DM6VOWQ): Small molecular drug
  Atovaquone (DMY4UMW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.38
  Bliss Independence Score: 8.38
  Loewe Additivity Score: 9.79
  LHighest Single Agent (HSA) Score: 9.85

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fomepizole

Disease Entry	ICD 11	Status	REF
Athylene glycol or methanol poisoning	NE61	Approved	[2]

Fomepizole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Alcohol dehydrogenase 1A (ADH1A)	TT5AHZ0	ADH1A_HUMAN	Modulator	[4]

Fomepizole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[5]

Fomepizole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Decreases Activity	[6]

Indication(s) of Atovaquone

Disease Entry	ICD 11	Status	REF
Fungal infection	1F29-1F2F	Approved	[3]

Atovaquone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[7]

Atovaquone 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]

Atovaquone Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydroorotate dehydrogenase (DHODH)	OTAKFN78	PYRD_HUMAN	Decreases Activity	[9]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Activity	[10]

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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole. Open Access Emerg Med. 2010 Aug 24;2:67-75.
• [6] Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet. 2011 Mar;36(1):1-16.
• [7] Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42.
• [8] Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis. Eur J Clin Pharmacol. 2002 Apr;58(1):19-27.
• [9] Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76.
• [10] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.