n(6)-(1-iminoethyl)lysine and Shock--Septic

Selective kinase inhibitors development is a cumbersome task because of ATP binding sites similarities across kinases. On contrast, irreversible allosteric covalent inhibition offers opportunity to develop novel selective kinase inhibitors. Previously, we reported thiazolidine-2,4-dione lead compounds eliciting in vitro irreversible allosteric inhibition of IKK-β. Herein, we address optimization into in vivo active anti-inflammatory agents. We successfully developed potent IKK-β inhibitors with the most potent compound eliciting IC

Topics: Allosteric Regulation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; I-kappa B Kinase; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Protein Kinase Inhibitors; RAW 264.7 Cells; Shock, Septic; Structure-Activity Relationship; Thiazolidinediones