PK/PD modeling of targeted protein degraders: Charting new waters and navigating the shallows DOI Creative Commons
Robin Thomas Ulrich Haid, Andreas Reichel

Drug Discovery Today, Год журнала: 2025, Номер unknown, С. 104311 - 104311

Опубликована: Фев. 1, 2025

The development of targeted protein degraders has picked up considerable steam recently, with interest stoked further by the first compounds entering Phase III studies. To keep leading biotech start-up firms, big pharma been keen to venture into this new field, bringing along experienced crews drug hunters. At their disposal, they find a burgeoning body literature on pharmacokinetics/pharmacodynamics (PK/PD) models tailor‑made for therapeutic modality. However, ocean opportunities might seem daunting even veteran scientists. Here, we provide orientation and direction researchers approach best suited respective questions.

Язык: Английский

Finding a needle in the haystack: ADME and pharmacokinetics/pharmacodynamics characterization and optimization toward orally available bifunctional protein degraders DOI
Giulia Apprato, Giulia Caron, Gauri Deshmukh

и другие.

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

Процитировано

1
PK/PD modeling of targeted protein degraders: Charting new waters and navigating the shallows DOI Creative Commons
Robin Thomas Ulrich Haid, Andreas Reichel

Drug Discovery Today, Год журнала: 2025, Номер unknown, С. 104311 - 104311

Опубликована: Фев. 1, 2025

The development of targeted protein degraders has picked up considerable steam recently, with interest stoked further by the first compounds entering Phase III studies. To keep leading biotech start-up firms, big pharma been keen to venture into this new field, bringing along experienced crews drug hunters. At their disposal, they find a burgeoning body literature on pharmacokinetics/pharmacodynamics (PK/PD) models tailor‑made for therapeutic modality. However, ocean opportunities might seem daunting even veteran scientists. Here, we provide orientation and direction researchers approach best suited respective questions.

Язык: Английский

Процитировано

0