Fig. 3: Chemical trends in primary screening.
From: Accelerating inhibitor discovery for deubiquitinating enzymes
a Heatmap representing potency and selectivity data for all 178 library compounds against 56 DUBs detected consistently over 80% of runs. b Electrophiles displayed diverse DUB hit rates. Acrylamides exhibited poor activity towards DUB catalytic cysteines. Insets adjacent to each bar indicate the number of hits and the total number of compounds containing each electrophile. c Presence and type of linker influenced compound activity and selectivity. d Individual warheads showed partially overlapping DUB target profiles. Venn diagram is colored by warhead, legend in figure. Bolded DUBs are hitherto untargeted. e, f Selected representative examples for multiple chemically similar hits for the same DUB from the screen. In the case of UCHL1, stringent requirements surrounding hydrogen bond acceptor position and amide orientation on the linker are highlighted in yellow. For VCPIP1, compounds were structurally similar except for the methylene group which moved along the backbone of the molecule (in blue). Moieties common across hits are highlighted for USP28 (in purple), USP3 (in red), and USP48 (in gray).
