Details of the Drug Combination

General Information of Drug Combination (ID: DC33KYA)

• Drug Combination Name: Hyodeoxycholic acid + Naltrexone
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Hyodeoxycholic acid (DMSIWD0): N.A.
  Naltrexone (DMUL45H): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.72
  Bliss Independence Score: 1.72
  Loewe Additivity Score: 4.76
  LHighest Single Agent (HSA) Score: 4.76

Molecular Interaction Atlas of This Drug Combination

Hyodeoxycholic acid Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A6 (UGT1A6)	DESD26P	UD16_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 2A3 (UGT2A3)	DEWBT6H	UD2A3_HUMAN	Metabolism	[10]

Indication(s) of Naltrexone

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[2]
Chronic alcoholism	6C40.2Z	Approved	[3]
Crohn disease	DD70	Approved	[4]
Gastroparesis	DA41.00	Approved	[4]
Inflammatory bowel disease	DD72	Approved	[4]
Obesity	5B81	Approved	[4]
Ulcerative colitis	DD71	Approved	[4]
Human immunodeficiency virus infection	1C62	Phase 4	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[6]
Chronic pain	MG30	Investigative	[4]

Naltrexone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Antagonist	[11]

Naltrexone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[12]

Naltrexone Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nitric oxide synthase, inducible (NOS2)	OTKKIOJ1	NOS2_HUMAN	Decreases Activity	[13]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[14]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[14]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Affects Response To Substance	[11]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Increases Response	[11]
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Affects Response To Substance	[15]
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)	OTAOZIGX	GBRB2_HUMAN	Affects Response To Substance	[16]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Affects Response To Substance	[16]
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6)	OTX4UC3O	GBRA6_HUMAN	Affects Response To Substance	[16]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 074918.
• [4] Naltrexone FDA Label
• [5] 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: 1639).
• [6] ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
• [7] Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
• [8] Isolation and characterization of hyodeoxycholic-acid: UDP-glucuronosyltransferase from human liver. Eur J Biochem. 1991 Sep 1;200(2):393-400. doi: 10.1111/j.1432-1033.1991.tb16197.x.
• [9] Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev. 1999 Nov;31(4):817-99.
• [10] Novel polymorphic human UDP-glucuronosyltransferase 2A3: cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction. Mol Pharmacol. 2008 Sep;74(3):744-54.
• [11] An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
• [12] In vivo chronic exposure to heroin or naltrexone selectively inhibits liver microsome formation of estradiol-3-glucuronide in the rat. Biochem Pharmacol. 2008 Sep 1;76(5):672-9.
• [13] Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4.
• [14] Chronic naltrexone treatment induces desensitization of the luteinizing hormone pulse generator for opioid blockade in hyperprolactinemic patients. J Clin Endocrinol Metab. 1995 May;80(5):1739-42. doi: 10.1210/jcem.80.5.7745028.
• [15] Association between the Stin2 VNTR polymorphism of the serotonin transporter gene and treatment outcome in alcohol-dependent patients. Alcohol Alcohol. 2008 Sep-Oct;43(5):516-22. doi: 10.1093/alcalc/agn048. Epub 2008 Jun 14.
• [16] Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.