General Information of Drug Combination (ID: DCBTS07)

Drug Combination Name
Naltrexone Artemisinin
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs Naltrexone   DMUL45H Artemisinin   DMOY7W3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 0.667
Bliss Independence Score: 0.215
Loewe Additivity Score: 1.271
LHighest Single Agent (HSA) Score: 1.556

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 Artemisinin
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [7]
Artemisinin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) TT3PQ2Y PYRD_PLAF7 Inhibitor [7]
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [7]
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Artemisinin Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [15]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [16]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [14]
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Artemisinin Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Activity [16]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [17]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [17]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [18]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [18]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [17]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [19]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A) OT5QQB5L IDH3A_HUMAN Decreases Expression [19]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [20]
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⏷ Show the Full List of 10 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 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
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 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
15 Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol. 1999 Oct;48(4):528-35.
16 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
17 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
18 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
19 Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
20 In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest. 2006 Sep;36(9):647-53. doi: 10.1111/j.1365-2362.2006.01700.x.