273404-37-8
中文名稱
N-(4-氨基-3-氯苯甲酰基)-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
英文名稱
(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
2025/01/07 01:01:17
273404-37-8 結(jié)構(gòu)式
基本信息
中文別名
化合物BELNACASANN-(4-氨基-3-氯苯甲酰基)-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
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 5級(jí)
N-(4-氨基-3-氯苯甲酰基)-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 3級(jí)
英文別名
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
所屬類別
生物化工：Caspase 抑制劑物理化學(xué)性質(zhì)
沸點(diǎn)779.0±60.0 °C(Predicted)
密度1.32
儲(chǔ)存條件-20°C
溶解度溶于DMSO(>25mg/ml)
酸度系數(shù)(pKa)12.60±0.40(Predicted)
形態(tài)固體
顏色灰白色至白色
穩(wěn)定性Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
常見問題列表
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.生物活性
Belnacasan (VX-765)是一種有效的選擇性caspase-1抑制劑，無細(xì)胞試驗(yàn)中Ki為0.8 nM。Phase 2。靶點(diǎn)
| Target | Value |
|
Caspase-4
(Cell-free assay) | <0.6 nM(Ki) |
|
Caspase-1
(Cell-free assay) | 0.8 nM(Ki) |
體外研究
VX-765是一種口服可吸收的VRT-043198前藥，其對(duì)ICE/caspase-1 和caspase-4表現(xiàn)出有效的抑制作用，Ki 分別為0.8 nM 和<0.6 nM。VRT-043198也會(huì)抑制IL-1β從PBMCs和全血中的釋放，IC50分別為0.67 μM 和1.9 μM。
體內(nèi)研究
在膠原誘導(dǎo)的關(guān)節(jié)炎小鼠模型中，VX-765 (200 mg/kg)抑制60% LPS誘導(dǎo)的IL-1β產(chǎn)生，并導(dǎo)致炎癥比例劑量依賴性顯著減少，對(duì)關(guān)節(jié)病變也能夠產(chǎn)生有效保護(hù)作用。在體內(nèi)，VX-765通過防止前腦星形膠質(zhì)細(xì)胞中IL-1β的增加阻斷大鼠體內(nèi)的癲癇發(fā)生，而對(duì)后放電持續(xù)時(shí)間沒有顯著影響。在急性癲癇小鼠模型中，VX-765 (50 mg/kg-200 mg/kg)通過延遲首次癲癇開始時(shí)間，并減少平均50%的癲癇發(fā)作次數(shù)以及64%的總持續(xù)時(shí)間，產(chǎn)生抗痙攣?zhàn)饔谩Ｔ诨加羞z傳性失神癲癇的成年大鼠體內(nèi)，VX-765藥物注射3天后，通過選擇性阻斷IL-1β生物合成，顯著降低累積持續(xù)時(shí)間和平均55%的棘慢波放電(SWDs)。