ArticleACS medicinal chemistry letters2022
When Cofactors Aren't X Factors: Functional Groups That Are Labile in Human Liver Microsomes in the Absence of NADPH.
Article in ACS medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
2 citing papers in PubMed.
- Charting New Territory: Systematic Evaluation of the Drug Potential ofJournal of medicinal chemistry · 2026Article
- Turning the Other Cheek: Influence of theACS medicinal chemistry letters · 2022Article
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Authors and funding
4 authors.
Funding
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Abstract
The metabolic stability of compounds is often assessed at an early stage in drug discovery programs by profiling with hepatic microsomes. Exclusion of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) in these assays provides insight into non-cytochrome P450 (CYP)-mediated metabolism. This report uses a matched molecular pair (MMP) application to assess which chemical substituents are commonly susceptible to non-NADPH-mediated metabolism by microsomes. The analysis found the overall prevalence of metabolism in the absence of NADPH to be low, with esters, amides, aldehydes, and oxetanes being among the most commonly susceptible functional groups. Given that non-CYP enzymes, such as esterases, may be expressed extrahepatically and lead to lower confidence in predicted pharmacokinetic profiles, an awareness of the functional groups that commonly undergo non-NADPH-mediated metabolism-as well as options for their replacement based on experimental MMP data-may help researchers derisk metabolic stability issues at an earlier stage in drug discovery.
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Registered trials
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