Details of the Drug Combination

General Information of Drug Combination (ID: DCFDKCK)

Drug Combination Name
MK-1439 Methadone
Indication
Disease Entry Status REF
Human Immunodeficiency Virus (HIV) Infection Phase 1 [1]
Component Drugs MK-1439   DM215WE Methadone   DMTW6IU
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-1439
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [2]
MK-1439 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human immunodeficiency virus Reverse transcriptase (HIV RT) TT84ETX POL_HV1B1 Inhibitor [2]
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MK-1439 Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [5]
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Indication(s) of Methadone
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [3]
Dry cough MD12 Approved [4]
Pain MG30-MG3Z Approved [3]
Methadone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor (OPR) TTN4QDT NOUNIPROTAC Agonist [6]
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Methadone Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Methadone Interacts with 10 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [8]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [8]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [11]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [8]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [8]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [8]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [8]
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⏷ Show the Full List of 10 DME(s)
Methadone Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [12]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Binding [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [14]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [14]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [15]
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References

1 ClinicalTrials.gov (NCT02715700) Effects of Doravirine (MK-1439) on Methadone Pharmacokinetics in Methadone-Maintained Participants (MK-1439-045)
2 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
3 Methadone FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Characterisation of the absorption, distribution, metabolism, excretion and mass balance of doravirine, a non-nucleoside reverse transcriptase inhibitor in humans. Xenobiotica. 2019 Apr;49(4):422-432.
6 Methadone treatment and its dangers. Medicina (Kaunas). 2009;45(5):419-25.
7 In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites. Pharmacology. 2007;80(4):304-11.
8 Methadone metabolism and drug-drug interactions: in vitro and in vivo literature review. J Pharm Sci. 2018 Dec;107(12):2983-2991.
9 Bidirectional transfer of methadone across human placenta. Biochem Pharmacol. 2005 Jan 1;69(1):187-97.
10 Methadone--metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004 Dec;50(6):551-9.
11 Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol. 1996 Mar;9(2):365-73.
12 Comparative effects of drugs on P-glycoprotein expression and activity using rat and human trophoblast models. Toxicol In Vitro. 2010 Mar;24(2):630-7. doi: 10.1016/j.tiv.2009.10.005. Epub 2009 Oct 17.
13 Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. doi: 10.1097/00008571-199610000-00004.
14 opioid receptor agonist-selective regulation of interleukin-4 in T lymphocytes. J Neuroimmunol. 2013 Oct 15;263(1-2):35-42. doi: 10.1016/j.jneuroim.2013.07.012. Epub 2013 Jul 25.
15 Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis. Biochim Biophys Acta. 2010 Nov;1802(11):1036-47. doi: 10.1016/j.bbadis.2010.07.024. Epub 2010 Aug 3.