The state of the art in secondary pharmacology and its impact on the safety of new medicines
Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities has become standard practice in pharmaceutical research and development, and regulatory agencies are increasingly requesting data on activity against targets with recognized adverse...
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| Veröffentlicht in: | Nature reviews. Drug discovery 2024-07, Vol.23 (7), p.525-545 |
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| creator | Brennan, Richard J. Jenkinson, Stephen Brown, Andrew Delaunois, Annie Dumotier, Bérengère Pannirselvam, Malar Rao, Mohan Ribeiro, Lyn Rosenbrier Schmidt, Friedemann Sibony, Alicia Timsit, Yoav Sales, Vicencia Toledo Armstrong, Duncan Lagrutta, Armando Mittlestadt, Scott W. Naven, Russell Peri, Ravikumar Roberts, Sonia Vergis, James M. Valentin, Jean-Pierre |
| description | Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities has become standard practice in pharmaceutical research and development, and regulatory agencies are increasingly requesting data on activity against targets with recognized adverse effect relationships. However, the screening strategies and target panels used by pharmaceutical companies may vary substantially. To help identify commonalities and differences, as well as to highlight opportunities for further optimization of secondary pharmacology assessment, we conducted a broad-ranging survey across 18 companies under the auspices of the DruSafe leadership group of the International Consortium for Innovation and Quality in Pharmaceutical Development. Based on our analysis of this survey and discussions and additional research within the group, we present here an overview of the current state of the art in secondary pharmacology screening. We discuss best practices, including additional safety-associated targets not covered by most current screening panels, and present approaches for interpreting and reporting off-target activities. We also provide an assessment of the safety impact of secondary pharmacology screening, and a perspective on opportunities and challenges in this rapidly developing field.
Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities is now standard practice in pharmaceutical research and development. This article uses a survey across 18 companies as the basis for discussing strategies for implementing secondary pharmacology screening programmes, approaches for interpreting off-target activities and which targets to include in screening panels, including several targets not commonly included in existing panels. |
| doi_str_mv | 10.1038/s41573-024-00942-3 |
| format | Article |
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Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities is now standard practice in pharmaceutical research and development. This article uses a survey across 18 companies as the basis for discussing strategies for implementing secondary pharmacology screening programmes, approaches for interpreting off-target activities and which targets to include in screening panels, including several targets not commonly included in existing panels.</description><identifier>ISSN: 1474-1776</identifier><identifier>ISSN: 1474-1784</identifier><identifier>EISSN: 1474-1784</identifier><identifier>DOI: 10.1038/s41573-024-00942-3</identifier><identifier>PMID: 38773351</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/436 ; 631/154/570 ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cancer Research ; Medicinal Chemistry ; Molecular Medicine ; Perspective ; Pharmaceutical industry ; Pharmacology ; Pharmacology/Toxicology ; R&D ; Research & development</subject><ispartof>Nature reviews. 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Drug discovery</title><addtitle>Nat Rev Drug Discov</addtitle><addtitle>Nat Rev Drug Discov</addtitle><description>Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities has become standard practice in pharmaceutical research and development, and regulatory agencies are increasingly requesting data on activity against targets with recognized adverse effect relationships. However, the screening strategies and target panels used by pharmaceutical companies may vary substantially. To help identify commonalities and differences, as well as to highlight opportunities for further optimization of secondary pharmacology assessment, we conducted a broad-ranging survey across 18 companies under the auspices of the DruSafe leadership group of the International Consortium for Innovation and Quality in Pharmaceutical Development. 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Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities is now standard practice in pharmaceutical research and development. 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| subjects | 631/154/436 631/154/570 Biomedical and Life Sciences Biomedicine Biotechnology Cancer Research Medicinal Chemistry Molecular Medicine Perspective Pharmaceutical industry Pharmacology Pharmacology/Toxicology R&D Research & development |
| title | The state of the art in secondary pharmacology and its impact on the safety of new medicines |
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