title: Lazaroids U83836E and U74389G are potent, time-dependent inhibitors of caspase-1.
abstract: Caspase-1 is involved in inflammatory processes and is overactive in autoimmunity and autoinflammation. Antioxidant small molecules also play a role in the immune response by decreasing inflammation. An 84-membered library of pro- and antioxidant small molecules was screened for potential inhibitors of caspase-1. Thirteen compounds were discovered to reduce the activity of caspase-1 below 30%. The most potent inhibitors were lazaroid antioxidant molecules, U83836E (B8) and U74389G (B9), displaying apparent Ki values of 48.0 and 50.0 nm, respectively. Both demonstrated a time-dependent and reversible inhibition.
authors: Department of Chemistry, DePaul University, 1110 W Belden Ave, Chicago, IL, 60614, USA.
authors: Margaret
authors: M
authors: Kawarski
authors: Department of Chemistry, DePaul University, 1110 W Belden Ave, Chicago, IL, 60614, USA.
authors: Thomas K
authors: TK
authors: Hagerman
authors: Department of Chemistry, DePaul University, 1110 W Belden Ave, Chicago, IL, 60614, USA.
authors: Caitlin E
authors: http://orcid.org/0000-0003-1249-7395
authors: CE
authors: Karver
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D054852:Small Molecule Libraries; D020170:Caspase 1
keywords: antioxidants; caspase-1; inhibitors; lazaroids; library screening