General Information of Drug Combination (ID: DCDI1WX)

Drug Combination Name
Naltrexone Tacrine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Naltrexone   DMUL45H Tacrine   DM51FY6
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 3.85
Bliss Independence Score: 3.85
Loewe Additivity Score: 18.11
LHighest Single Agent (HSA) Score: 18.13

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [8]
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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 [9]
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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 [10]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [11]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [11]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Affects Response To Substance [8]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Increases Response [8]
Sodium-dependent dopamine transporter (SLC6A3) OT39XG28 SC6A3_HUMAN Affects Response To Substance [12]
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2) OTAOZIGX GBRB2_HUMAN Affects Response To Substance [13]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Affects Response To Substance [13]
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6) OTX4UC3O GBRA6_HUMAN Affects Response To Substance [13]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Tacrine
Disease Entry ICD 11 Status REF
Alzheimer disease 8A20 Approved [7]
Tacrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Acetylcholinesterase (AChE) TT1RS9F ACES_HUMAN Inhibitor [14]
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Tacrine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]
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Tacrine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [16]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [17]
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Tacrine Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cholinesterase (BCHE) OTOH3WQ9 CHLE_HUMAN Decreases Activity [18]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Decreases Activity [19]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Decreases Activity [20]
Ribosyldihydronicotinamide dehydrogenase (NQO2) OTGDAJRZ NQO2_HUMAN Decreases Activity [20]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [21]
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Decreases Activity [22]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Decreases Activity [23]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [24]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [25]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases ADR [26]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Response To Substance [27]
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⏷ Show the Full List of 12 DOT(s)

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 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: 6687).
8 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.
9 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.
10 Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4.
11 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.
12 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.
13 Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.
14 Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int J Clin Pract Suppl. 2002 Jun;(127):6-19.
15 Tacrine sinusoidal uptake and biliary excretion in sandwich-cultured primary rat hepatocytes. J Pharm Pharm Sci. 2014;17(3):427-38.
16 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
17 Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther. 2000 Apr;67(4):432-7.
18 Comparative effects of cationic triarylmethane, phenoxazine and phenothiazine dyes on horse serum butyrylcholinesterase. Arch Biochem Biophys. 2008 Oct 15;478(2):201-5.
19 Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Chem Biol Interact. 2013 Mar 25;203(1):226-30.
20 Reduction and scavenging of chemically reactive drug metabolites by NAD(P)H:quinone oxidoreductase 1 and NRH:quinone oxidoreductase 2 and variability in hepatic concentrations. Chem Res Toxicol. 2018 Feb 19;31(2):116-126.
21 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
22 Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes. Eur J Pharmacol. 1989 Nov 28;173(1):53-64. doi: 10.1016/0014-2999(89)90008-3.
23 Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. doi: 10.1016/s1074-5521(03)00071-1.
24 High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.
25 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
26 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.
27 Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab Dispos. 2011 Aug;39(8):1388-95. doi: 10.1124/dmd.110.037077. Epub 2011 May 3.