Maciag Monika, Karamyan Vardan T
Department of Foundational Medical Studies, William Beaumont School of Medicine, Oakland University, Rochester, Michigan 48309, United States.
J Med Chem. 2025 Apr 24;68(8):7854-7865. doi: 10.1021/acs.jmedchem.4c02228. Epub 2025 Apr 2.
Pharmacological profiling is critical for the development of safe drugs. With increasing awareness of its significance and attempts to share best practices, here we aimed to understand how pharmacological profiling is implemented and reported in the primary literature by analyzing the representation of nonkinase enzymes in selectivity screens. This aspect has been overlooked in previous publications, despite enzymes constituting a significant portion of the pharmacological targets for currently marketed drugs. Our analysis shows that while industry recommendations for improved pharmacological profiling have been widely adopted, enzymes remain largely underrepresented: about a quarter of studies did not include enzymes, and on average, enzymes comprise only 11% of all targets in pharmacological screens. We discuss possible reasons for this shortcoming and provide examples of critical enzymes missing from current screens. We conclude with the notion that selectivity screens should be expanded to include more enzymes to improve drug development and safety.
药理特征分析对于安全药物的研发至关重要。随着对其重要性的认识不断提高以及分享最佳实践的尝试，我们旨在通过分析选择性筛选中非激酶酶的呈现情况，了解在主要文献中如何实施和报告药理特征分析。尽管酶构成了当前上市药物药理靶点的很大一部分，但这一方面在以前的出版物中被忽视了。我们的分析表明，虽然业界关于改进药理特征分析的建议已被广泛采用，但酶在很大程度上仍未得到充分体现：约四分之一的研究未包括酶，并且平均而言，酶在药理筛选中仅占所有靶点的11%。我们讨论了这一缺陷的可能原因，并提供了当前筛选中缺失的关键酶的示例。我们得出的结论是，应扩大选择性筛选以纳入更多酶，以改善药物研发和安全性。
