Z-VAD(OH)-FMK
(Synonyms: Z-VAD(OH)-FMK) 目录号 : GC45189
Z-VAD(OH)-FMK是所有半胱天冬酶的不可逆三肽抑制剂。
Cas No.:161401-82-7
Sample solution is provided at 25 µL, 10mM.
Z-VAD(OH)-FMK is an irreversible tripeptide inhibitor of all caspases[1]. Z-VAD(OH)-FMK is the unmethylated form of Z-VAD-FMK. Z-VAD(OH)-FMK inhibits the apoptosis process by covalently binding to the active site of caspase and preventing its activation, and can be used to study apoptosis-related immune responses [2].
In vitro, Z-VAD(OH)-FMK (50μM) treatment of Panc-1 and MIAPaca-2 cells for 1 hour effectively inhibited Rhein-induced cell death[3]. Z-VAD(OH)-FMK (0-100μM) treatment of T cells dose-dependently inhibited cell proliferation without blocking the processing of caspase-8 and caspase-3 proteins[4]. Z-VAD-FMK (40μM) treatment of HeLa cells for 30 minutes inhibited TSSLT-induced apoptosis[5].
In vivo, Z-VAD(OH)-FMK (3mg/kg) can inhibit caspase activation and prevent myocardial contractile dysfunction and cardiomyocyte apoptosis through intravenous injection in rats with endotoxin injury[6]. Z-VAD(OH)-FMK (1.5 mg/kg) was combined with carfilzomib to treat C26 adenocarcinoma cells inoculated mice, resulting in an increase in caspase-3 and BAX levels and a decrease in BCL-XL levels in the gastrocnemius muscle, regulating protein levels in the renin-angiotensin system[7].
References:
[1] Davies C W, Chaney J, Korbel G, et al. The co-crystal structure of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) with a tripeptide fluoromethyl ketone (Z-VAE (OMe)-FMK)[J]. Bioorganic & medicinal chemistry letters, 2012, 22(12): 3900-3904.
[2] Rajah T, Chow S C. The inhibition of human T cell proliferation by the caspase inhibitor z-VAD-FMK is mediated through oxidative stress[J]. Toxicology and applied pharmacology, 2014, 278(2): 100-106.
[3] Liu Y, Shi C, He Z, et al. Inhibition of PI3K/AKT signaling via ROS regulation is involved in Rhein-induced apoptosis and enhancement of oxaliplatin sensitivity in pancreatic cancer cells[J]. International Journal of Biological Sciences, 2021, 17(2): 589.
[4] Lawrence C P, Chow S C. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties[J]. Toxicology and applied pharmacology, 2012, 265(1): 103-112.
[5] Liu H R, Peng X D, He H B, et al. Antiproliferative activity of the total saponin of Solanum lyratum Thunb in Hela cells by inducing apoptosis[J]. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 2008, 63(11): 836-842.
[6] NEVIÈRE R, FAUVEL H, CHOPIN C, et al. Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis[J]. American journal of respiratory and critical care medicine, 2001, 163(1): 218-225.
[7] Wang Q, Li C, Peng X, et al. Combined treatment of carfilzomib and z-VAD-fmk inhibits skeletal proteolysis and apoptosis and ameliorates cancer cachexia[J]. Medical oncology, 2015, 32: 1-10.
Z-VAD(OH)-FMK是所有半胱天冬酶的不可逆三肽抑制剂[1]。Z-VAD(OH)-FMK是Z-VAD-FMK的非甲基化形式。Z-VAD(OH)-FMK通过与半胱天冬酶的活性位点共价结合，阻止其活化，从而抑制细胞凋亡过程，可用于研究细胞凋亡相关的免疫反应[2]。
在体外，Z-VAD(OH)-FMK（50μM）处理Panc-1和MIAPaca-2细胞1h，有效抑制了莱茵（Rhein ）诱导的细胞死亡[3]。Z-VAD(OH)-FMK（0-100μM）处理T细胞，可剂量依赖性地抑制细胞增殖，但不阻断caspase-8和caspase-3蛋白的加工[4]。Z-VAD-FMK（40μM）处理HeLa细胞30min，抑制了TSSLT诱导的细胞凋亡[5]。
在体内，Z-VAD(OH)-FMK（3mg/kg）通过静脉注射治疗内毒素损伤大鼠，可以抑制半胱天冬酶激活，预防心肌收缩功能障碍和心肌细胞凋亡[6]。Z-VAD(OH)-FMK（1.5mg/kg）通过和卡非佐米联合治疗C26腺癌细胞接种小鼠，导致腓肠肌中caspase-3和BAX水平升高，BCL-XL水平降低，调节了肾素-血管紧张素系统中的蛋白质水平[7]。
Cell experiment [1]: | |
Cell lines | Panc-1、MIAPaCa-2 cells |
Preparation method | Panc-1 and MIAPaCa-2 cells were treated with or without Z-VAD(OH)-FMK (50 μM) for 1 h and then with 100 μM lysate for 24 h. |
Reaction Conditions | 50μM; 1 h |
Applications | The pan-caspase inhibitor Z-VAD(OH)-FMK strongly prevented PC cells from Rhein-induced cell death. |
Animal experiment [2]: | |
Animal models | Adult male SD rats |
Preparation method | Adult male SD rats were housed for 6 d in groups of six in standard cages and supplied ad libitum with laboratory chow and tap water. Treatments were administered intravenously, via the dorsal penine vein, after brief ether anesthesia. Z-VAD(OH)-FMK and z-FA.fmk were dissolved in DMSO 20mg/ml and a 3mg/kg dose was injected in 500μl saline. Sham-treated and endotoxin-treated rats were injected, respectively, with 500μl saline and 10mg/kg of endotoxin. |
Dosage form | 3mg/kg; i.v. |
Applications | Z-VAD(OH)-FMK admininistration prevented myocardial systolic dysfunction and apoptosis when studied 4 h and even 14 h after endotoxin administration. |
References: [1] Liu Y, Shi C, He Z, et al. Inhibition of PI3K/AKT signaling via ROS regulation is involved in Rhein-induced apoptosis and enhancement of oxaliplatin sensitivity in pancreatic cancer cells[J]. International Journal of Biological Sciences, 2021, 17(2): 589. [2] NEVIÈRE R, FAUVEL H, CHOPIN C, et al. Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis[J]. American journal of respiratory and critical care medicine, 2001, 163(1): 218-225. | |
| Cas No. | 161401-82-7 | SDF | |
| 别名 | Z-VAD(OH)-FMK | ||
| Canonical SMILES | O=C(O)C[C@@H](C(CF)=O)NC([C@H](C)NC([C@H](C(C)C)NC(OCC1=CC=CC=C1)=O)=O)=O | ||
| 分子式 | C21H28FN3O7 | 分子量 | 453.5 |
| 溶解度 | DMSO: 5 mg/ml | 储存条件 | 4°C, away from moisture and light |
| 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2051 mL | 11.0254 mL | 22.0507 mL |
| 5 mM | 0.441 mL | 2.2051 mL | 4.4101 mL |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.2051 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。
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Quality Control & SDS
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- Purity: >98.00%
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