Fundamental aspects of DMPK optimization of targeted protein degraders

Autor:	Carina Cantrill, Caroline Rynn, Prasoon Chaturvedi, Matthias B. Wittwer, Isabelle Walter, Jeannine Petrig Schaffland
Rok vydání:	2019
Předmět:	0301 basic medicine Pharmacology Computer science Drug discovery Computational biology Myotonin-Protein Kinase Small Molecule Libraries 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Neoplasms Drug Discovery Animals Humans
Zdroj:	Drug discovery today. 25(6)
ISSN:	1878-5832
Popis:	Targeted protein degraders are an emerging modality. Their properties fall outside the traditional small-molecule property space and are in the 'beyond rule of 5' space. Consequently, drug discovery programs focused on developing orally bioavailable degraders are expected to face complex drug metabolism and pharmacokinetics (DMPK) challenges compared with traditional small molecules. Nevertheless, little information is available on the DMPK optimization of oral degraders. Therefore, in this review, we discuss our experience of these DMPK optimization challenges and present methodologies and strategies to overcome the hurdles dealing with this new small-molecule modality, specifically in developing oral degraders to treat cancer.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74104587d87ed6b150aa547e3e449e59 https://pubmed.ncbi.nlm.nih.gov/32298797 Zobrazit plný text záznamu Full Text from ScienceDirect