Finding a needle in the haystack: ADME and pharmacokinetics/pharmacodynamics characterization and optimization toward orally available bifunctional protein degraders

Expert Opinion on Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Фев. 16, 2025

Degraders are an increasingly important sub-modality of small molecules as illustrated by ever-expanding number publications and clinical candidate in human trials. Nevertheless, their preclinical optimization ADME PK/PD properties has remained challenging. Significant research efforts being directed to elucidate underlying principles derive rational strategies. In this review the authors summarize current best practices terms vitro assays vivo experiments. Furthermore, collate comment on understanding optimal physicochemical characteristics impact absorption, distribution, metabolism excretion including knowledge Drug-Drug interactions. Finally, describe Pharmacokinetic prediction Pharmacokinetic/Pharmacodynamic -concepts unique degraders how implement these projects. Despite many recent advances field, continued will further our design regarding degrader optimization. Machine-learning computational approaches become once larger, more robust datasets available. tissue-targeting (particularly Central Nervous System be studied efficacious drug regimens that capitalize catalytic mode action. additional specialized (e.g. covalent degraders, LOVdegs) can enrich field offer interesting alternative approaches.

Язык: Английский

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In silico modeling of targeted protein degradation

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117432 - 117432

Опубликована: Фев. 20, 2025

Язык: Английский

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Computational approaches to aid PROTAC drug discovery

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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