Potency assay (off target):
Within the target family:
SGC DUB panel comprising 10 individual USPs tested at 10 and 50 uM showing strong inhibition of USP21 and less than 50% inhibition for seven other DUBs of the panel. USP10 and USP22 showed about 50% residual DUB activity.
Outside Target family:
afety screen against 70 individual off-targets, including enzymes, receptors, transporter, ion channels, etc. at 10 uM with with only acetylcholine esterase and adenosine transporters being inhibited with 72% (IC50 = 7.61 μM) and 62%, respectively.
DUBprofiler (Ubiquigent) across 44 individual DUB targets at 1 and 10 μM concentrations. BAY-805 showed very low activity (<15% inhibition) across various DUBs, and 91 and 88% inhibition of USP21 at 10 and 1 μM concentrations.
also tested in-house against six cysteine proteases (all IC50 > 20 μM) and in a kinase selectivity panel (Eurofins/Panlabs) against more than 360 kinases at 10 μM concentration showing minor inhibitory activity of BAY-805 for PRAK(h) (58% inhibition, IC50 = 8.6 μM) and TrkA(h) (57% inhibition, IC50 > 10 μM).
