Bachovchin, Daniel A. published the artcileSuperfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening, Quality Control of 50670-76-3, the publication is Proceedings of the National Academy of Sciences of the United States of America (2010), 107(49), 20941-20946, S20941/1-S20941/172, database is CAplus and MEDLINE.
Serine hydrolases (SHs) are-one of the largest and most diverse enzyme classes in mammals. They play fundamental roles in virtually all physiol. processes and are targeted by drugs to treat diseases such as diabetes, obesity, and neurodegenerative disorders. Despite this, we lack biol. understanding for most of the 110+ predicted mammalian metabolic SHs, in large part because of a dearth of assays to assess their biochem. activities and a lack of selective inhibitors to probe their function in living systems. We show here that the vast majority (>80%) of mammalian metabolic SHs can be labeled in proteomes by a single, active site-directed fluorophosphonate probe. We exploit this universal activity-based assay in a library-vs.-library format to screen 70+ SHs against 140+ structurally diverse carbamates. Lead inhibitors were discovered for ∼40% of the screened enzymes, including many poorly characterized SHs: Global profiles identified carbamate inhibitors that discriminate among highly sequence-related SHs and, conversely, enzymes that share inhibitor sensitivity profiles despite lacking sequence homol. These findings indicate that sequence relatedness is not a strong predictor of shared pharmaol. within the SH superfamily. Finally, we show that lead carbamate inhibitors can be optimized into pharmacol. probes that inactivate individual SHs with high specificity in vivo.
Proceedings of the National Academy of Sciences of the United States of America published new progress about 50670-76-3. 50670-76-3 belongs to esters-buliding-blocks, auxiliary class Benzene,Phenol,Ester, name is Ethyl 4′-hydroxy-[1,1′-biphenyl]-4-carboxylate, and the molecular formula is C15H14O3, Quality Control of 50670-76-3.
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https://en.wikipedia.org/wiki/Ester,
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