Methylpyrrole inhibitors of BET bromodomains
- PMID: 28268136
- DOI: 10.1016/j.bmcl.2017.02.057
Methylpyrrole inhibitors of BET bromodomains
Abstract
An NMR fragment screen for binders to the bromodomains of BRD4 identified 2-methyl-3-ketopyrroles 1 and 2. Elaboration of these fragments guided by structure-based design provided lead molecules with significant activity in a mouse tumor model. Further modifications to the methylpyrrole core provided compounds with improved properties and enhanced activity in a mouse model of multiple myeloma.
Keywords: BET proteins; Bromodomain; Fragment screening.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Chemical Information