Details of the Drug Combination

General Information of Drug Combination (ID: DCTEL6A)

• Drug Combination Name: Auranofin + Raltegravir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Auranofin (DMWE2N4): Small molecular drug
  Raltegravir (DMYURI6): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.87
  Bliss Independence Score: 2.87
  Loewe Additivity Score: 3.95
  LHighest Single Agent (HSA) Score: 4

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 Raltegravir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]

Raltegravir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Modulator	[3]

Raltegravir Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[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] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [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] Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012 Jun;56(6):2959-66. doi: 10.1128/AAC.05424-11. Epub 2012 Feb 27.
• [8] Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen. Drug Metabol Drug Interact. 2011;26(3):139-41.
• [9] Exposure-related effects of atazanavir on the pharmacokinetics of raltegravir in HIV-1-infected patients. Ther Drug Monit. 2010 Dec;32(6):782-6.