Details of the Drug Combination

General Information of Drug Combination (ID: DCKJWHD)

• Drug Combination Name: Lefaxin + Fomepizole
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Lefaxin (DM0CEY3): Small molecular drug
  Fomepizole (DM6VOWQ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.64
  Bliss Independence Score: 9.64
  Loewe Additivity Score: 11.66
  LHighest Single Agent (HSA) Score: 11.67

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lefaxin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Lefaxin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[2]

Lefaxin Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[4]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Expression	[5]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[5]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[5]
Glutathione peroxidase 1 (GPX1)	OTE2O72Q	GPX1_HUMAN	Decreases Expression	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[5]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[5]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[6]

Indication(s) of Fomepizole

Disease Entry	ICD 11	Status	REF
Athylene glycol or methanol poisoning	NE61	Approved	[3]

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	[7]

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	[8]

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	[9]

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] Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
• [3] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [4] In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases. Chem Biol Interact. 2011 Apr 25;190(2-3):79-83.
• [5] The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells. Toxicol In Vitro. 2019 Oct;60:237-244.
• [6] Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Arch Toxicol. 2002 May;76(4):203-8. doi: 10.1007/s00204-002-0328-8. Epub 2002 Mar 9.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole. Open Access Emerg Med. 2010 Aug 24;2:67-75.
• [9] 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.