Details of the Drug Combination

General Information of Drug Combination (ID: DC08NAV)

• Drug Combination Name: Auranofin + Lefaxin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Auranofin (DMWE2N4): Small molecular drug
  Lefaxin (DM0CEY3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.44
  Bliss Independence Score: 3.44
  Loewe Additivity Score: 4.68
  LHighest Single Agent (HSA) Score: 4.69

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Auranofin

Disease Entry	ICD 11	Status	REF
Inflammatory arthritis	FA2Z	Approved	[2]

Auranofin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid hormone receptor ERR (ESRR)	TTP3UTW	ERR1_HUMAN; ERR2_HUMAN; ERR3_HUMAN	Modulator	[4]

Auranofin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[5]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[5]

Auranofin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Metallothionein-1A (MT1A)	OTKBH52X	MT1A_HUMAN	Increases ADR	[6]

Indication(s) of Lefaxin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

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	[3]

Lefaxin Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[7]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Expression	[8]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[8]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[8]
Glutathione peroxidase 1 (GPX1)	OTE2O72Q	GPX1_HUMAN	Decreases Expression	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[8]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[8]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[8]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[8]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[8]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[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] 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: 6306).
• [3] Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Selection and characterization of a human ovarian cancer cell line resistant to auranofin. Oncotarget. 2017 Oct 9;8(56):96062-96078.
• [6] 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.
• [7] In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases. Chem Biol Interact. 2011 Apr 25;190(2-3):79-83.
• [8] The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells. Toxicol In Vitro. 2019 Oct;60:237-244.
• [9] 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.