273404-37-8
中文名称
N-(4-氨基-3-氯苯甲酰基)-3-甲基-L-缬氨酰-N-[(2R,3S)-2-乙氧基四氢-5-氧代-3-呋喃基]-L-脯氨酰胺
英文名称
(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide
CAS
273404-37-8
分子式
C24H33ClN4O6
分子量
508.995
MOL 文件
273404-37-8.mol
更新日期
2024/04/28 11:56:09
273404-37-8 结构式
基本信息
中文别名
化合物BELNACASANN-(4-氨基-3-氯苯甲酰基)-3-甲基-L-缬氨酰-N-[(2R,3S)-2-乙氧基四氢-5-氧代-3-呋喃基]-L-脯氨酰胺
N-(4-氨基-3-氯苯甲酰基)-3-甲基-L-缬氨酰-N-[(2R,3S)-2-乙氧基四氢-5-氧代-3-呋喃基]-L-脯氨酰胺 5级
N-(4-氨基-3-氯苯甲酰基)-3-甲基-L-缬氨酰-N-[(2R,3S)-2-乙氧基四氢-5-氧代-3-呋喃基]-L-脯氨酰胺 3级
英文别名
BelnacasanCS-387
VX-765，VX 765
Belnacasan (VX765)
VX-765(Belnacasan)
BELNACASAN
VX-765
VX 765
Caspase-1-4 Inhibitor VX-765
VX 765
VX-765
VX765. BELNACASAN
(S)-1-((S)-2-(4-Amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrah
N-(4-Amino-3-chlorobenzoyl)-3-methyl-L-valyl-N-[(2R,3S)-2-ethoxytetrahydro-5-oxo-3-furanyl]-L-prolinamide
所属类别
生物化工：Caspase 抑制剂物理化学性质
沸点779.0±60.0 °C(Predicted)
密度1.32
储存条件-20°C
溶解度溶于DMSO(>25mg/ml)
酸度系数(pKa)12.60±0.40(Predicted)
形态固体
颜色灰白色至白色
稳定性Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
常见问题列表
生物活性
VX-765是一种有效的选择性的caspase-1抑制剂， Ki为0.8 nM。Phase 2。体外研究
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.体内研究
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.生物活性
Belnacasan (VX-765)是一种有效的选择性caspase-1抑制剂，无细胞试验中Ki为0.8 nM。Phase 2。靶点
| Target | Value |
|
Caspase-4
(Cell-free assay) | <0.6 nM(Ki) |
|
Caspase-1
(Cell-free assay) | 0.8 nM(Ki) |
体外研究
VX-765是一种口服可吸收的VRT-043198前药，其对ICE/caspase-1 和caspase-4表现出有效的抑制作用，Ki 分别为0.8 nM 和<0.6 nM。VRT-043198也会抑制IL-1β从PBMCs和全血中的释放，IC50分别为0.67 μM 和1.9 μM。
体内研究
在胶原诱导的关节炎小鼠模型中，VX-765 (200 mg/kg)抑制60% LPS诱导的IL-1β产生，并导致炎症比例剂量依赖性显著减少，对关节病变也能够产生有效保护作用。在体内，VX-765通过防止前脑星形胶质细胞中IL-1β的增加阻断大鼠体内的癫痫发生，而对后放电持续时间没有显著影响。在急性癫痫小鼠模型中，VX-765 (50 mg/kg-200 mg/kg)通过延迟首次癫痫开始时间，并减少平均50%的癫痫发作次数以及64%的总持续时间，产生抗痉挛作用。在患有遗传性失神癫痫的成年大鼠体内，VX-765药物注射3天后，通过选择性阻断IL-1β生物合成，显著降低累积持续时间和平均55%的棘慢波放电(SWDs)。