Fragment-based target screening as an empirical approach to prioritising targets: a case study on antibacterials.
Journal
Drug discovery today
ISSN: 1878-5832
Titre abrégé: Drug Discov Today
Pays: England
ID NLM: 9604391
Informations de publication
Date de publication:
10 Sep 2020
10 Sep 2020
Historique:
received:
22
01
2020
revised:
27
07
2020
accepted:
03
09
2020
pubmed:
14
9
2020
medline:
14
9
2020
entrez:
13
9
2020
Statut:
aheadofprint
Résumé
Here, we describe a novel workflow combining informatic and experimental approaches to enable evidence-based prioritising of targets from large sets in parallel. High-throughput protein production and biophysical fragment screening is used to identify those targets that are tractable and ligandable. As proof of concept we have applied this to a set of antibacterial targets comprising 146 essential genes. Of these targets, 51 were selected and 38 delivered results that allowed us to rank them by ligandability. The data obtained against these derisked targets have enabled rapid progression into structurally enabled drug discovery projects, demonstrating the practical value of the fragment-based target screening workflow.
Identifiants
pubmed: 32920060
pii: S1359-6446(20)30339-1
doi: 10.1016/j.drudis.2020.09.003
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.