ArticleACS medicinal chemistry letters2014
Structure-Activity Studies Reveal the Oxazinone Ring Is a Determinant of Cytochrome P450 2B6 Activity Toward Efavirenz.
Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 15 citations in OpenAlex.
- Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry.Drug metabolism and disposition: the biological fate of chemicals · 2019Review
- Halogen Substitution Influences Ketamine Metabolism by Cytochrome P450 2B6: In Vitro and Computational Approaches.Molecular pharmaceutics · 2019Article
- Efavirenz and Efavirenz-like Compounds Activate Human, Murine, and Macaque Hepatic IRE1Molecular pharmacology · 2019Article
- Crystal Structure of CYP2B6 in Complex with an Efavirenz Analog.International journal of molecular sciences · 2018Article
- Single Heteroatom Substitutions in the Efavirenz Oxazinone Ring Impact Metabolism by CYP2B6.ChemMedChem · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 2B6 (CYP2B6) is primarily responsible for the metabolism of the anti-HIV drug efavirenz (EFV). We set out to explore the molecular basis for CYP2B6 activity toward EFV by examining the metabolism of eight EFV analogues. cDNA-expressed CYP2B6 formed monooxygenated metabolites from EFV analogues containing an intact oxazinone or oxazine ring, but not from analogues with a disrupted ring, suggesting this ring is important for metabolism of EFV by CYP2B6. Subsequent substrate depletion analysis of EFV and EFV analogues found to be CYP2B6 substrates revealed further differences between these CYP2B6 substrates. Compounds that were not found to be CYP2B6 substrates were still able to inhibit CYP2B6 activity toward a known substrate, bupropion, suggesting they do gain access to the CYP2B6 active site. Taken together, these data reveal structural characteristics of EFV, namely, the oxazinone ring, that are critical for CYP2B6 metabolism of compounds with the EFV chemical scaffold.
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Registered trials
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