Fundamental aspects of DMPK optimization of targeted protein degraders.
Journal
Drug discovery today
ISSN: 1878-5832
Titre abrégé: Drug Discov Today
Pays: England
ID NLM: 9604391
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
04
12
2019
revised:
03
03
2020
accepted:
16
03
2020
pubmed:
17
4
2020
medline:
1
9
2021
entrez:
17
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32298797
pii: S1359-6446(20)30119-7
doi: 10.1016/j.drudis.2020.03.012
pii:
doi:
Substances chimiques
Small Molecule Libraries
0
Myotonin-Protein Kinase
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
969-982Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.