VX-765
(Synonyms: Belnacasan; 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; VX-765) 目录号 : GC12725
VX-765 是一种新开发的选择性小分子 caspase-1 抑制剂，可通过血脑屏障并在体外和体内减少炎症。
Cas No.:273404-37-8
Sample solution is provided at 25 µL, 10mM.
VX-765 is a newly developed, selective, small molecule caspase-1 inhibitor that can pass the blood-brain barrier and reduce inflammation in vitro and in vivo[1].
VX-765 potently and specifically inhibited human Casp1 (IC50 3.68 nM)[2]. Increases of autophagy-related proteins were detected in VX-765-pretreated human umbilical mesenchymal stem cells(HUMSCs), indicating the potential of VX-765 for up-regulating autophagy. Meanwhile, increased p-AMPK and decreased p-mTOR were detected in VX-765-pretreated HUMSCs. Furthermore, the anti-inflammatory and anti-apoptosis effect of VX-765 could be abolished by an autophagy inhibitor or AMPK inhibitor[3]
In vivo，VX-765 ameliorated renal dysfunction, tubular injury, and renal inflammation in mice with DN, but had no effect on blood glucose level or body weight, illustrating that VX-765 represents a novel and efficacious therapeutic treatment for DN without increasing the risk of hypoglycemia in diabetic patients[4]
References:
[1]. Boxer MB, Quinn AM, et al. A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety. ChemMedChem. 2010 May 3;5(5):730-8.
[2]. Flores J, No l A, et al. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model. Nat Commun. 2018 Sep 25;9(1):3916.
[3]. Sun Z, Gu L, et al. VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway. CNS Neurosci Ther. 2020 Sep;26(9):952-961.
[4]. Wen S, Deng F, et al. VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation. J Diabetes Investig. 2022 Jan;13(1):22-33.
VX-765 是一种新开发的选择性小分子 caspase-1 抑制剂，可通过血脑屏障并在体外和体内减少炎症[1]。
VX-765 有效且特异性地抑制人 Casp1 (IC50 3.68 nM)[2]。在 VX-765 预处理的人脐带间充质干细胞 (HUMSCs) 中检测到自噬相关蛋白的增加，表明 VX-765 具有上调自噬的潜力。同时，在 VX-765 预处理的 HUMSC 中检测到增加的 p-AMPK 和减少的 p-mTOR。此外，VX-765 的抗炎和抗凋亡作用可被自噬抑制剂或 AMPK 抑制剂消除[3]
在体内，VX-765 改善了 DN 小鼠的肾功能障碍、肾小管损伤和肾脏炎症，但对血糖水平或体重没有影响，表明 VX-765 代表了一种新型有效的 DN 治疗方法不会增加糖尿病患者发生低血糖的风险[4]
| Cell experiment [1]: | |
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Cell lines |
human umbilical mesenchymal stem cells(HUMSCs) |
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Preparation Method |
MTT assay was used to test the toxicity of VX-765. Oxygen-glucose deprivation (OGD) was applied to mimic ischemic environment in vitro experiments, and The apoptosis of HUMSCs incubated with VX-765 was assessed 12 or 24 hours after OGD exposure. |
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Reaction Conditions |
10µM VX-765 for 12, 24h. |
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Applications |
Compared to OGD groups, TUNEL-positive cells, IL-1β, and IL-6 decreased while IL-10 increased in VX-765+OGD group. The result demonstrate the anti-apoptosis and anti- inflammatory role of VX-765 in HUMSCs. |
| Animal experiment [2]: | |
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Animal models |
CD1 (ICR) mice |
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Preparation Method |
CD1 (ICR) mice were injected intraperitoneally with 55 mg/kg streptozotocin(STZ). Mice with blood glucose level over 300 mg/dL were considered diabetic.Diabetic mice were administered with VX-765 for 8 weeks.The treatment with VX-765 was initiated 2 weeks after STZ injection |
|
Dosage form |
100mg/kg VX-765, intraperitoneal(i.p.) injection |
|
Applications |
Administration of VX-765 in diabetic mice effectively ameliorated renal function, compared with that of untreated diabetic mice.VX-765 treatment did not affect blood glucose level or body weight, illustrating that VX-765 ameliorated diabetic nephropathy independent of its metabolic effects. |
|
References: [1]. Sun Z, Gu L, et al. VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway. CNS Neurosci Ther. 2020 Sep;26(9):952-961. [2]. Wen S, Deng F, et al. VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation. J Diabetes Investig. 2022 Jan;13(1):22-33. |
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| Cas No. | 273404-37-8 | SDF | |
| 别名 | Belnacasan; 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; VX-765 | ||
| 化学名 | (2S)-1-[(2S)-2-[(4-amino-3-chlorobenzoyl)amino]-3,3-dimethylbutanoyl]-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]pyrrolidine-2-carboxamide | ||
| Canonical SMILES | CCOC1C(CC(=O)O1)NC(=O)C2CCCN2C(=O)C(C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl | ||
| 分子式 | C24H33ClN4O6 | 分子量 | 508.99 |
| 溶解度 | ≥ 313 mg/mL in DMSO, ≥ 50.5 mg/mL in EtOH with ultrasonic | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9647 mL | 9.8234 mL | 19.6468 mL |
| 5 mM | 0.3929 mL | 1.9647 mL | 3.9294 mL |
| 10 mM | 0.1965 mL | 0.9823 mL | 1.9647 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Related Biological Data
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VX-765 (50 mg/kg) (GlpBio, USA) was administered intraperitoneally 1 h before liver IRI.
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Related Biological Data
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