ArticleSLAS discovery : advancing life sciences R & D2024
Consideration of vendor-related differences in hepatic metabolic stability data to optimize early ADME screening in drug discovery.
Article in SLAS discovery : advancing life sciences R & D, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 3 citations in OpenAlex.
- Assessing the impact of data harmonization on human liver microsomal stability prediction model performance.Results in chemistry · 2026Article
- Comparative analysis of sex-based, vendor-based, and species differences in cytochrome P450 metabolism.Scientific reports · 2026Article
- The Enzyme-Bag Platform for Cytochrome P450 Biotransformation and High-Throughput Drug Metabolism Screening.Methods in molecular biology (Clifton, N.J.) · 2026Article
- In Vitro Pharmacokinetic Profiling of Thiourea Derivatives of Naproxen With Anti-Inflammatory and Anticancer Activity.Chemistry & biodiversity · 2026Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic metabolic stability is a crucial determinant of oral bioavailability and plasma concentrations of a compound, and its measurement is important in early drug discovery. Preliminary metabolic stability estimations are commonly performed in liver microsomal fractions. At the National Center for Advancing Translational Sciences, a single-point assay in rat liver microsomes (RLM) is employed for initial stability assessment (Tier I) and a multi-point detailed stability assay is employed as a Tier II assay for promising compounds. Although the in vitro and in vivo metabolic stability of compounds typically exhibit good correlation, conflicting results may arise in certain cases. While investigating one such instance, we serendipitously found vendor-related RLM differences in metabolic stability and metabolite formation, which had implications for in vitro and in vivo correlations. In this study, we highlight the importance of considering vendor differences in hepatic metabolic stability data and discuss strategies to avoid these pitfalls.
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Registered trials
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