VX-765
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
VX-765,VRT-043198的口服吸收前药,是有效的Caspase-1选择性抑制剂,属于ICE/caspase-1亚族caspases。
Caspase-1,被称为白介素(IL)1转换酶,负责关键的炎性介质IL-1β的加工,使其无活性前体转换为具活性的分泌蛋白。据报道,针对细胞内细菌,Caspase-1介导快速的细胞死亡程序,在巨噬细胞中被称为程序性细胞死亡[1]。
VX-765通常被代谢为活性分子VRT-043198。在细菌产物刺激的外周血单核细胞培养物中,VRT-043198抑制IL-1β和IL-18释放,但对其它细胞因子的分泌没有影响,如IL-α、TNFα、IL-6和IL-8[2]。
此产品也用于其它模型来检验Caspase-1的功能。在类风湿性关节炎和皮肤炎症的小鼠模型中,口服VX-765显著降低疾病的严重程度以及炎症细胞因子和趋化因子的分泌[1]。此外,最近的研究表明,在感染HIV的淋巴组织中,VX-765剂量依赖性地防止CD4 T细胞程序性死亡[3]。
参考文献:
1. Denes A, Lopez-Castejon G, Brough D. Caspase-1: is IL-1 just the tip of the ICEbergCell Death Dis 2012,3:e338.
2.Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, et al. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoy l)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther 2007,321:509-516.
3.Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 2014,505:509-514.
- 1. YULIN YUAN, CAIPING ZHANG, et al. "Curcumin improves the function of umbilical vein endothelial cells by inhibiting H2O2‑induced pyroptosis." Mol Med Rep. 2022 Jun;25(6):214. PMID: 35543146
- 2. Hila Israelov, Orly Ravid, et al. "Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair." J Neuroinflammation 2020 Sep 9;17(1):267. PMID: 32907600
- 3. Darren C. Johnson, Marian C. Okondo, et al. "DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes." Cell Death Dis. 2020 Aug 14;11(8):628. PMID: 32796818
- 4. Panina SB, Baran N, et al. "A mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs." Cell Death Dis. 2019 Aug 13;10(8):617. PMID: 31409768
- 5. Yang G, Wang J, et al. "White spot syndrome virus infection activates Caspase 1-mediated cell death in crustacean." Virology. 2018 Dec 13;528:37-47. PMID: 30554072
Physical Appearance | A solid |
Storage | Desiccate at -20°C |
M.Wt | 508.99 |
Cas No. | 273404-37-8 |
Formula | C24H33ClN4O6 |
Solubility | insoluble in H2O; ≥313 mg/mL in DMSO; ≥50.5 mg/mL in EtOH with ultrasonic |
Chemical Name | (2S)-1-[(2S)-2-[(4-amino-3-chlorobenzoyl)amino]-3,3-dimethylbutanoyl]-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]pyrrolidine-2-carboxamide |
SDF | Download SDF |
Canonical SMILES | CCOC1C(CC(=O)O1)NC(=O)C2CCCN2C(=O)C(C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验 [1]: | |
蛋白酶试验 |
通过测定底物水解速率评估酶抑制程度。使用对硝基苯胺或氨甲基香豆素 (AMC) 标记的底物,如:ICE/caspase-1,suc-YVAD-对硝基苯胺;caspase-4,Ac-WEHD-AMC;caspase-6,Ac-VEID-AMC;caspase-3,caspase-7,caspase-8,和caspase-9,Ac-DEVD-AMC;颗粒酶B,Ac-IEPD-AMC。将酶和底物加入到反应缓冲液中 [10 mM Tris,pH 7.5,0.1% (w/v) CHAPS,1 mM 二硫苏糖醇以及5% (v/v) 二甲基亚砜],置于37 °C下孵育10分钟。将甘油8% (v/v)加入caspase-3、caspase-6、caspase-9 和颗粒酶B的缓冲液中,以提高酶的稳定性。使用荧光计测定底物水解速率。 |
动物实验 [1]: | |
动物模型 |
胶原诱导性关节炎 (CIA) 小鼠模型 |
给药剂量 |
10、25、50或100 mg/kg;口服给药;每日2次,持续24天 |
实验结果 |
在CIA小鼠模型中,VX-765显著地呈剂量依赖性地减少炎症分数。此外,100 mg/kg VX-765与5 mg/kg Prednisolone具有相同的效果。 |
其它注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: [1]. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, et al. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoy l)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther 2007,321:509-516. |
VX-765是一种新型的Caspase-1抑制剂,被研究用于癫痫的治疗,目前正由Vertex开发。 | ||||||
靶点 | Caspase-1 | |||||
IC50 |
质量控制和MSDS
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