Tracing Potential Covalent Inhibitors of an E3 Ubiquitin Ligase through Target-Focused Modelling.

ABSTRACT: The Nedd4-1 E3 Ubiquitin ligase has been implicated in multiple disease conditions due its overexpression. Although the enzyme may be targeted both covalently and non-covalently, minimal studies provide effective inhibitors against it. Recently, research has focused on covalent inhibitors based on their characteristic, highly-selective warheads and ability to prevent drug resistance. This prompted us to screen for new covalent inhibitors of Nedd4-1 using a combination of computational approaches. However, this task proved challenging due to the limited number of electrophilic moieties available in virtual libraries. Therefore, we opted to divide an existing covalent Nedd4-1 inhibitor into two parts: a non-covalent binding group and a pre-selected α, β-unsaturated ester that forms the coval

SUBMITTER: Bjij I 

PROVIDER: S-EPMC6749425 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature