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Lazaroids U83836E and U74389G are Potent, Time‐Dependent Inhibitors of Caspase‐1
Author(s) -
Kawarski Margaret,
Hagerman Thomas K.,
Karver Caitlin E.
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12572
Subject(s) - chemistry , antioxidant , caspase 3 , inflammation , pharmacology , caspase , small molecule , immune system , apoptosis , biochemistry , biology , immunology , programmed cell death
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 K i values of 48.0 and 50.0 n m , respectively. Both demonstrated a time‐dependent and reversible inhibition.