Bachovchin_2010_Bioorg.Med.Chem.Lett_20_2254

Reference

Title : Oxime esters as selective, covalent inhibitors of the serine hydrolase retinoblastoma-binding protein 9 (RBBP9) - Bachovchin_2010_Bioorg.Med.Chem.Lett_20_2254
Author(s) : Bachovchin DA , Wolfe MR , Masuda K , Brown SJ , Spicer TP , Fernandez-Vega V , Chase P , Hodder PS , Rosen H , Cravatt BF
Ref : Bioorganic & Medicinal Chemistry Lett , 20 :2254 , 2010
Abstract :

We recently described a fluorescence polarization platform for competitive activity-based protein profiling (fluopol-ABPP) that enables high-throughput inhibitor screening for enzymes with poorly characterized biochemical activity. Here, we report the discovery of a class of oxime ester inhibitors for the unannotated serine hydrolase RBBP9 from a full-deck (200,000+ compound) fluopol-ABPP screen conducted in collaboration with the Molecular Libraries Screening Center Network (MLSCN). We show that these compounds covalently inhibit RBBP9 by modifying enzyme's active site serine nucleophile and, based on competitive ABPP in cell and tissue proteomes, are selective for RBBP9 relative to other mammalian serine hydrolases.

PubMedSearch : Bachovchin_2010_Bioorg.Med.Chem.Lett_20_2254
PubMedID: 20207142
Gene_locus related to this paper: human-RBBP9

Related information

Inhibitor ML114
Gene_locus ML114    human-RBBP9
Family ML114    human-RBBP9    Hydrolase_RBBP9_YdeN

Citations formats

Bachovchin DA, Wolfe MR, Masuda K, Brown SJ, Spicer TP, Fernandez-Vega V, Chase P, Hodder PS, Rosen H, Cravatt BF (2010)
Oxime esters as selective, covalent inhibitors of the serine hydrolase retinoblastoma-binding protein 9 (RBBP9)
Bioorganic & Medicinal Chemistry Lett 20 :2254

Bachovchin DA, Wolfe MR, Masuda K, Brown SJ, Spicer TP, Fernandez-Vega V, Chase P, Hodder PS, Rosen H, Cravatt BF (2010)
Bioorganic & Medicinal Chemistry Lett 20 :2254