Z-DEVD-FMK
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.
Z-DEVD-FMK是一种选择性的caspase-3抑制剂,是一个四肽。Z-DEVD-FMK被广泛用于急性损伤的体外和体内模型,表明caspase-3在神经细胞死亡中的作用。在CCI和缺氧处理之后,脑实质内注射Z-DEVD-FMK可以减少病灶大小。
Z-DEVD-FMK是一种有效的calpain抑制剂,用Z-DEVD-FMK治疗后观察到的结果部分反映了这一作用。Z-DEVD-FMK的早期治疗可以改善神经功能,减少病变体积。在无细胞实验中,Z-DEVD-FMK抑制calpain的活性。在体外坏死模型中,Z-DEVD-FMK可以减少细胞死亡。在体内模型中,TBI处理之后,Z-DEVD-FMK治疗可以抑制calpain的活性。在几乎没有caspase-3激活的以坏死性神经细胞死亡为主的损伤中,Z-DEVD-FMK可以改善神经功能,减少组织损伤。而且Z-DEVD-FMK的有效治疗与calpain介导的血影蛋白(spectrin)降解的减少相关联。在由maitotoxin诱导的坏死性神经元细胞死亡体外模型中,Z-DEVD-FMK以低于抑制caspase-3的浓度处理时仍然具有神经保护作用。
在以坏死为主的TBI模型中,在损伤后一小时之内用Z-DEVD-FMK处理可以改善行为恢复,减少组织损伤,阻止calpain介导的α-血影蛋白降解产物的积累。在体外,Z-DEVD-FMK也可以减少坏死性神经元细胞死亡,这种神经保护效应与calpain的抑制相关联,而非caspase 3或cathepsin B。此外,Z-DEVD-FMK可以减少calpain介导的casein的水解,这表明Z-DEVD-FMK可以直接抑制calpain。Z-DEVD-FMK的这种非特异性的属性可以部分解释它的神经保护效应 [5]。
参考文献:
1. Garcia-Calvo M, Peterson EP, Leiting B, Ruel R, Nicholson DW, Thornberry NA (1998) Inhibition of human caspases by peptidebased and macromolecular inhibitors. J Biol Chem 273:32608–32613
2. Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW (1997) A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 272:17907–17911
3. Yakovlev AG, Knoblach SM, Fan L, Fox GB, Goodnight R, Faden AI (1997) Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J Neurosci 17:7415–7424
4. Clark RS, Kochanek PM, Watkins SC, Chen M, Dixon CE, Seidberg NA, Melick J, Loeffert JE, Nathaniel PD, Jin KL, Graham SH (2000) Caspase-3 mediated neuronal death after traumatic brain injury in rats. J Neurochem 74:740–753
5. S. M. Knoblach, D. A. Alroy et al, Caspase Inhibitor z-DEVD-fmk Attenuates Calpain and Necrotic Cell Death in Vitro and After Traumatic Brain Injury, Journal of Cerebral Blood Flow & Metabolism 24:1119–1132
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Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 668.66 |
Cas No. | 210344-95-9 |
Formula | C30H41N4O12F |
Synonyms | Caspase-3 Inhibitor II,Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-FMK |
Solubility | insoluble in H2O; insoluble in EtOH; ≥60 mg/mL in DMSO |
Chemical Name | methyl (4S)-5-[[(2S)-1-[[(3S)-5-fluoro-1-methoxy-1,4-dioxopentan-3-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-[[(2S)-4-methoxy-4-oxo-2-(phenylmethoxycarbonylamino)butanoyl]amino]-5-oxopentanoate |
SDF | Download SDF |
Canonical SMILES | CC(C)C(C(=O)NC(CC(=O)OC)C(=O)CF)NC(=O)C(CCC(=O)OC)NC(=O)C(CC(=O)OC)NC(=O)OCC1=CC=CC=C1 |
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。 |
细胞实验[1]: | |
细胞系 |
WM9、WM35、WM98-1和WM793细胞 |
溶解方法 |
在DMSO中的溶解度 >10 mM。为了获得更高的浓度,可以将离心管在37°C加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20°C以下储存几个月。 |
反应条件 |
20 μM,24小时 |
应用 |
为了说明caspase激活在TRAIL诱导的细胞凋亡中的重要性,Z-DEVD-FMK连同TRAIL一起加入到黑色素瘤细胞中,Z-DEVD-FMK仅能部分抑制TRAIL的细胞毒性作用。Z-DEVD-FMK抑制细胞死亡能力的下降可能是由于该多肽进入细胞的能力。 |
动物实验[2]: | |
动物模型 |
可控皮层碰撞(CCI)损伤的雄性C57Bl/6小鼠 |
剂量 |
160 ng;脑室注射 |
应用 |
为了评估运动恢复,检测小鼠在超过21天的康复期间穿过狭窄挂梁的能力。在损伤后第7、14和21天,在CCI后1小时用Z-DEVD-FMK处理的小鼠表现比对照组显著更好。而在CCI后4小时用Z-DEVD-FMK处理的小鼠仅在损伤后第21天的表现比对照组显著更好。而在任何其它测试天中,它们并没有表现出比其它治疗组更好的趋势。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Griffith T S, Chin W A, Jackson G C, et al. Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. The Journal of Immunology, 1998, 161(6): 2833-2840. [2] Knoblach S M, Alroy D A, Nikolaeva M, et al. Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury. Journal of Cerebral Blood Flow & Metabolism, 2004, 24(10): 1119-1132. |
Z-DEVD-FMK是一种细胞通透性的、不可逆的Caspase-3/CPP32抑制剂,也能不可逆的抑制Caspase-6、Caspase-7、caspase-8和Caspase-10。. | ||||||
靶点 | Caspase-3 | Caspase-6 | Caspase-7 | Caspase-8 | Caspase-10 | |
IC50 |
质量控制和MSDS
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