Details of the Drug Combination

General Information of Drug Combination (ID: DCWVTLB)

• Drug Combination Name: Baclofen + Auranofin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Baclofen (DM0QV1J): Small molecular drug
  Auranofin (DMWE2N4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 7.29
  Bliss Independence Score: 7.29
  Loewe Additivity Score: 8.74
  LHighest Single Agent (HSA) Score: 8.82

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Baclofen

Disease Entry	ICD 11	Status	REF
Multiple sclerosis	8A40	Approved	[2]
Fragile X syndrome	LD55	Phase 3	[3]

Baclofen Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gamma-aminobutyric acid B receptor (GABBR)	TTDCVZW	GABR1_HUMAN; GABR2_HUMAN	Modulator	[5]

Baclofen Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[6]
Adenosine receptor A1 (ADORA1)	OTI7X39E	AA1R_HUMAN	Increases ADR	[7]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Increases Transport	[8]

Indication(s) of Auranofin

Disease Entry	ICD 11	Status	REF
Inflammatory arthritis	FA2Z	Approved	[4]

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	[9]

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	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]

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	[7]

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: 1084).
• [3] ClinicalTrials.gov (NCT01706523) Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders. U.S. National Institutes of Health.
• [4] 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).
• [5] Synthesis and pharmacology of the baclofen homologues 5-amino-4-(4-chlorophenyl)pentanoic acid and the R- and S-enantiomers of 5-amino-3-(4-chlorop... J Med Chem. 1999 Jun 3;42(11):2053-9.
• [6] Anti-inflammatory effects of the GABA(B) receptor agonist baclofen in allergic contact dermatitis. Exp Dermatol. 2010 Jul 1;19(7):661-6. doi: 10.1111/j.1600-0625.2010.01076.x. Epub 2010 Feb 25.
• [7] 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.
• [8] Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Selection and characterization of a human ovarian cancer cell line resistant to auranofin. Oncotarget. 2017 Oct 9;8(56):96062-96078.