BAY-805

BAY-805 is an inhibitor of ubiquitin-specific protease 21 (USP21, IC50 = 6 nM in a homogenous time-resolved fluorescence (HTRF) assay). It is selective for USP21 over a panel of 44 deubiquitinases (DUBs) and 68 other enzymes, receptors, transporters, and ion channels at 10 µM but does inhibit acetylcholinesterase (AChE) and adenosine transporters by 72 and 62%, respectively. BAY-805 is also selective for USP21 over a panel of six cysteine proteases (IC50s = >20 µM for all) and a panel of greater than 360 kinases at 10 µM but does inhibit MAPK-activated protein kinase 5 (MAPKAPK5), also known as p38-regulated/activated protein kinase (PRAK, IC50 = 8.6 µM). It induces activation of NF-kappaB in a reporter assay using HEK293T cells (EC50 = 17 nM). BAY-805 reduces spheroid formation in HCT-15 and HT-29 colon cancer cells (IC50s = 1.6 and 7.5 µM, respectively). In vivo, BAY-805 (5 and 10 mg/kg) decreases disease severity and spleen, liver, kidney, and lung viral titers in a mouse model of enterovirus 71 (EV71) infection. SMILES O=C([C@@H](CC(C)C)NC(C1(C(F)(F)F)CCCCC1)=O)NC2=NN=C(CC3=CC=C(C#N)C=C3)S2 InChi Code InChI=1S/C24H28F3N5O2S/c1-15(2)12-18(29-21(34)23(24(25,26)27)10-4-3-5-11-23)20(33)30-22-32-31-19(35-22)13-16-6-8-17(14-28)9-7-16/h6-9,15,18H,3-5,10-13H2,1-2H3,(H,29,34)(H,30,32,33)/t18-/m1/s1 InChi Key LXRBPWHQMGKMRT-GOSISDBHSA-N