title: Novel irreversible caspase-1 inhibitor attenuates the maturation of intracellular interleukin-1beta.
abstract: Caspase-1, the most efficient enzyme in processing the proinflammatory cytokines interleukin 1beta and interleukin 18 in humans, is associated with inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and some neuronal diseases. We previously reported that isoquinoline-1,3,4-trione and its derivatives are novel caspase-3 inhibitors that could attenuate apoptosis in vitro and in vivo. Here we report a novel derivative of isoquinoline-1,3,4-trione that is highly potent in inhibiting caspase-1 activity in an irreversible and slow-binding manner, thus inhibiting cellular caspase-1 activity and the maturation of interleukin 1beta in U-937 cells.
authors.affiliation: East China Normal Univeristy, Academy of Life Science, P.R. China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Ma
authors.forename: Hua-Jie
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Zhang
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Jun-Qing
authors.initials: JQ
authors.lastname: Du
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Li
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
authors.forename: Jia
authors.initials: J
authors.lastname: Li
mesh_terms: D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D053583:Interleukin-1beta; D007546:Isoquinolines; C515844:isoquinoline-1,3,4-trione; D020170:Caspase 1