Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening.

ABSTRACT: Inosine 5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for the production of guanine nucleotides. Disruption of IMPDH activity has been explored as a therapeutic strategy for numerous purposes, such as for anticancer, immunosuppression, antiviral, and antimicrobial therapy. In the present study, we established a luciferase-based high-throughput screening system to identify IMPDH inhibitors from our chemical library of known bioactive small molecules. The screening of 1400 compounds resulted in the discovery of three irreversible inhibitors: disulfiram, bronopol, and ebselen. Each compound has a distinct chemical moiety that differs from other reported IMPDH inhibitors. Further evaluation revealed that these compounds are potent inhibitors of IMPDHs with k_on values

SUBMITTER: Sarwono AEY 

PROVIDER: S-EPMC6249553 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature