N-(4-氨基-3-氯苯甲?；?-3-甲基-L-纈氨酰-N-[(2R,3S
發(fā)布者：信康 瀏覽次數(shù)：
產(chǎn)品名稱:N-(4-氨基-3-氯苯甲?；?-3-甲基-L-纈氨酰-N-[(2R,3S)-2-乙氧基四氫-5-氧代-3-呋喃基]-L-脯氨酰胺CAS:273404-37-8別名：N-(4-氨基-3-氯苯甲?；?-3-甲基-L-纈氨酰-N-[(2R,3S)-2-乙氧基四氫-5-氧代-3-呋喃基]-L-脯氨酰胺英文名：(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide
- 生物活性VX-765是一種有效的選擇性的caspase-1抑制劑， Ki為0.8 nM。Phase 2。
- 體外研究VX-765 is an orally absorbed prodrug of VRT-043198, which exhibits potent inhibition against ICE/caspase-1 and caspase-4 with Ki of 0.8 nM and less than 0.6 nM, respectively. And VRT-043198 also inhibits IL-1β release from both PBMCs and whole blood with IC50 of 0.67 μM and 1.9 μM, respectively.
- 體內(nèi)研究In collagen-induced arthritis mouse model, VX-765 (200 mg/kg) inhibits LPS-induced IL-1β production by about 60%, and results in a dose-dependent, statistically significant reduction in the inflammation scores and effective protection from joint changes. In vivo, VX-765 blocks kindling epileptogenesis in rats by preventing IL-1β increase in forebrain astrocytes without significant effect on afterdischarge duration. In the mouse model of acute seizures, VX-765 (50 mg/kg-200 mg/kg) produces the anticonvulsant effect by delaying the time to onset of the first seizure and decreasing the number of seizures as well as their total duration by average 50% and 64%. In adult rats with genetic absence epilepsy (GAERS), VX-765, after the 3rd drug injection, significantly reduces the cumulative duration and number of spike-and-wave discharges (SWDs) by 55% on average by selectively blocking IL-1β biosynthesis.
- 特征VX-765 is a potent and selective inhibitor of interleukin-converting enzyme/caspase-1.
