General Information of Drug Combination (ID: DCBHRFK)

Drug Combination Name
Atovaquone Naltrexone
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs Atovaquone   DMY4UMW Naltrexone   DMUL45H
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: 1.882
Bliss Independence Score: 0.767
Loewe Additivity Score: 7.164
LHighest Single Agent (HSA) Score: 7.728

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Atovaquone
Disease Entry ICD 11 Status REF
Fungal infection 1F29-1F2F Approved [2]
Atovaquone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) TT3PQ2Y PYRD_PLAF7 Inhibitor [8]
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Atovaquone Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
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Atovaquone Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydroorotate dehydrogenase (DHODH) OTAKFN78 PYRD_HUMAN Decreases Activity [10]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Activity [11]
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Indication(s) of Naltrexone
Disease Entry ICD 11 Status REF
Alcohol dependence 6C40.2 Approved [3]
Chronic alcoholism 6C40.2Z Approved [4]
Crohn disease DD70 Approved [5]
Gastroparesis DA41.00 Approved [5]
Inflammatory bowel disease DD72 Approved [5]
Obesity 5B81 Approved [5]
Ulcerative colitis DD71 Approved [5]
Human immunodeficiency virus infection 1C62 Phase 4 [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [7]
Chronic pain MG30 Investigative [5]
Naltrexone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor (OPR) TTN4QDT NOUNIPROTAC Antagonist [12]
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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 [13]
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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 [14]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [15]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [15]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Affects Response To Substance [12]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Increases Response [12]
Sodium-dependent dopamine transporter (SLC6A3) OT39XG28 SC6A3_HUMAN Affects Response To Substance [16]
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2) OTAOZIGX GBRB2_HUMAN Affects Response To Substance [17]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Affects Response To Substance [17]
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6) OTX4UC3O GBRA6_HUMAN Affects Response To Substance [17]
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⏷ Show the Full List of 9 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 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 074918.
5 Naltrexone FDA Label
6 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).
7 ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
8 Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42.
9 Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis. Eur J Clin Pharmacol. 2002 Apr;58(1):19-27.
10 Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76.
11 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.
12 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.
13 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.
14 Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4.
15 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.
16 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.
17 Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.