Journal
DRUG DISCOVERY TODAY
Volume 25, Issue 10, Pages 1793-1800Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2020.07.013
Keywords
-
Categories
Ask authors/readers for more resources
Proteolysis-targeting chimeras (PROTACs) are an emerging therapeutic modality with the potential to open target space not accessible to conventional small molecules via a degradation-based mechanism; however, their bifunctional nature can result in physicochemical properties that breach commonly accepted limits for small-molecule oral drugs. We offer a drug metabolism and pharmacokinetics (DMPK) perspective on the optimisation of oral PROTACs across a diverse set of projects within Oncology R&D at AstraZeneca, highlighting some of the challenges that they have presented to our established screening cascade. Furthermore, we challenge some of the perceptions and dogma surrounding the feasibility of oral PROTACS and demonstrate that acceptable oral PK properties for this modality can be regularly achievable despite the physicochemical property challenges they present.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available