Fig. 1: Fluorescence-based screen to identify first-in-class JAMM inhibitors.
From: Molecular glues that inhibit deubiquitylase activity and inflammatory signaling
a, Left, schematic of a TAMRA-linked IQF diubiquitin substrate. Ub, ubiquitin. Right, reaction progress curve of BRISC DUB activity. Data points are the mean ± s.e.m. of two independent experiments carried out in technical duplicate. b, Z-score normalization of 320 compounds from an in-house kinase-directed inhibitor library and identification of hit compounds in wells H20 and P12. c, Chemical structures of AT7519 and two isomers with an additional 2,6-dichlorobenzoyl moiety. d, Dose–response inhibition of BRISC activity by the H20 compound and the two potential isomers, AP-5-144 and JMS-175-2. e, Dose–response inhibition of trypsin, USP2 and JAMM/MPN DUB enzymes AMSH*, BRISC, ARISC and BRCC36–Abraxas 2 by JMS-175-2. f, Chemical structure of the FX-171-C compound. g, As in e, but for FX-171-C. Data points in d,e,g are the mean ± s.e.m. of three independent experiments carried out in technical duplicate.
