Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA, USA.
Non-clinical Development, Bill and Melinda Gates Medical Research Institute, Cambridge, MA, USA.
Drug Metab Rev. 2024 Aug;56(3):223-246. doi: 10.1080/03602532.2024.2370331. Epub 2024 Jul 5.
With contributions from colleagues across academia and industry, we have put together the annual reviews of research advances on drug biotransformation and bioactivation since 2016 led by Cyrus Khojasteh. While traditional small molecules and biologics are still predominant in drug discovery, we start to notice a paradigm shift toward new drug modalities (NDMs) including but not limited to peptide and oligonucleotide therapeutics, protein degraders (heterobifunctional degraders and molecule glues), conjugated drugs and covalent inhibitors. The readers can learn more on each new drug modality from several recent comprehensive reviews (Blanco et al. 2022; Hillebrand et al. 2024; Phuna et al. 2024). Based on this trend, we put together this stand-alone review branched from our previous efforts (Baillie et al. 2016; Khojasteh et al. 2023) with a focus on the metabolism of NDMs. We collected 11 articles which exemplify recent discoveries and perspectives in this field.
在学术界和工业界同仁的共同努力下,我们整理了自 2016 年以来由 Cyrus Khojasteh 领导的关于药物生物转化和生物活化研究进展的年度综述。虽然传统的小分子和生物制剂仍然在药物发现中占主导地位,但我们开始注意到一种向新模式药物(NDMs)的范式转变,包括但不限于肽和寡核苷酸治疗药物、蛋白降解剂(杂双功能降解剂和分子胶)、偶联药物和共价抑制剂。读者可以从最近的几篇综合评论(Blanco 等人,2022 年;Hillebrand 等人,2024 年;Phuna 等人,2024 年)中了解到每种新模式药物的更多信息。基于这一趋势,我们从之前的努力(Baillie 等人,2016 年;Khojasteh 等人,2023 年)中整理了这篇独立的综述,重点关注 NDMs 的代谢。我们收集了 11 篇文章,这些文章体现了该领域的最新发现和观点。