The Missing Enzymes: A Call to Update Pharmacological Profiling Practices for Better Drug Safety Assessment

Document Type

Article

Publication Date

4-24-2025

Publication Title

Journal of Medicinal Chemistry

Abstract

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.

Volume

68

Issue

8

First Page

7854

Last Page

7865

DOI

10.1021/acs.jmedchem.4c02228

ISSN

1520-4804

PubMed ID

40173276

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