Ac-DEVD-CHO

Caspase 3 (Ki = 0.23 nM); Caspase-8 (Ki = 0.92 nM); Caspase-7 (Ki = 1.6 nM); Caspase-10 (Ki = 12 nM); Caspase-1 (Ki = 18 nM); Caspase-6 (Ki = 31 nM); Caspase-9 (Ki = 60 nM); Caspase-4 (Ki = 132 nM); Caspase-5 (Ki = 205 nM); Caspase-2 (Ki = 1710 nM)

Ac-DEVD-CHO 是一种有效的 caspase-3 抑制剂 (Ki = 230 pM)。相比之下，这种醛仅轻微抑制 caspase-2 (Ki = 1.7 μM)，并且对四肽底物的裂解效果较差。 Ac-DEVD-CHO 的 Ki 值范围为 1 至 300 nM，可显着抑制 III 族半胱天冬酶 [1]。即使在缺血发作后施用，Ac-DEVD-CHO'caspase-3抑制也能显着改善离体工作心脏大鼠模型中受损心肌的缺血后收缩恢复。 Ac-DEVD-CHO 的保护机制似乎独立于细胞凋亡而发挥作用。 Ac-DEVD-CHO[2] 不抑制肌钙蛋白 I 裂解。

在 MI 时接受 Ac-DEVD-CHO 会导致幼龄动物心肌细胞中活化的 caspase-3 表达降低 61% (p<0.05)，心肌细胞凋亡降低 84%。然而，Caspase 抑制对衰老小鼠的心肌细胞凋亡或激活的 caspase-3 表达没有影响[4]。 Ac-DEVD-CHO 抑制和/或推迟大鼠感光细胞损伤的发展，并减缓携带 rd 基因的小鼠的疾病进展，这些小鼠通常在生命的早期经历视网膜变性[2]。

对半胱氨酸蛋白酶半胱天冬酶家族的肽基和大分子抑制剂的研究有助于确定这些酶在炎症和哺乳动物凋亡中的中心作用。由于对这些分子的选择性的不完全理解，对这些研究的清晰解释受到了损害。在这里，我们描述了几种基于肽的抑制剂和水痘血清蛋白CrmA对10种人半胱天冬酶的选择性。所检测的肽醛（Ac-WEHD-CHO、Ac-DEVD-CHO，Ac-YVAD-CHO和叔丁氧羰基-IETD-CHO）包括几种含有各种胱天蛋白酶的最佳四肽识别基序的肽醛。这些醛对这些酶表现出广泛的选择性和潜力，离解常数范围从75 pM到>10μM。卤代甲基酮苄氧羰基VAD氟甲基酮是一种特异性广泛的不可逆胱天蛋白酶抑制剂，其二阶失活率范围为胱天蛋白酶2的2.9 x 10（2）M-1 s-1至胱天蛋白酶1的2.8 x 10（5）M-1 s-1。用基于肽的抑制剂获得的结果与先前描述的底物特异性研究预测的结果一致。牛痘血清蛋白CrmA是I组半胱天冬酶（胱天蛋白酶-1、-4和-5）和大多数III组半胱天蛋白酶（胱天酶-8、-9和-10）的有效（Ki<20nM）和选择性抑制剂，表明该病毒通过抑制细胞凋亡和宿主炎症反应促进感染[1]。

OCL 与 RANKL 一起孵育，并用 0.5 mM SIN 处理 24 小时，无论有或没有特定的 caspase-3 抑制剂 Ac-DEVD-CHO (10 μM)。处理后，用 PBS 冲洗细胞并用 10 μM Hoechst 33258 染料染色 15 分钟。荧光显微镜用于拍摄染色细胞的照片。通过计数每孔中出现凋亡核浓缩的细胞数量，测量差异[4]。

One hundred and two male mice are subjected to cecal ligation and puncture or sham operation. The animals are assigned into three equal groups (n=34) according to random number table: sham group, model group, and caspase-3 inhibitor (CI) group. Thirty minutes before CLP, Ac-DEVD-CHO (4 μg/g) is injected subcutaneously in CI group. The levels of blood urea nitrogen (BUN) and creatinine (Cr) are determined, and the concentrations of tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-10) are measured by enzyme linked immunosorbent assay (ELISA), the renal cell apoptosis rate is determined by flow cytometry. The 4-day and 7-day survival rates of three groups of mice are observed[5].

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3 mg/kg; i.p.

C57Bl6 mice.

[1]. J Biol Chem . 1998 Dec 4;273(49):32608-13.

[2]. J Am Coll Cardiol . 2001 Dec;38(7):2063-70.

[3]. Mol Cell Biol . 2006 Nov;26(21):7880-91.

[4]. Cardiovasc Ther . 2013 Dec;31(6):e102-10.

[5] Acta Histochem. 2003, 36(4):263-270.

Ac-Asp-Glu-Val-Asp-H is a tetrapeptide consisting of two L-aspartic acid residues, an L-glutamyl residue and an L-valine residue with an acetyl group at the N-terminal and with the C-terminal carboxy group reduced to an aldehyde. It is an inhibitor of caspase-3/7. It has a role as a protease inhibitor.

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Studies with peptide-based and macromolecular inhibitors of the caspase family of cysteine proteases have helped to define a central role for these enzymes in inflammation and mammalian apoptosis. A clear interpretation of these studies has been compromised by an incomplete understanding of the selectivity of these molecules. Here we describe the selectivity of several peptide-based inhibitors and the coxpox serpin CrmA against 10 human caspases. The peptide aldehydes that were examined (Ac-WEHD-CHO, Ac-DEVD-CHO, Ac-YVAD-CHO, t-butoxycarbonyl-IETD-CHO, and t-butoxycarbonyl-AEVD-CHO) included several that contain the optimal tetrapeptide recognition motif for various caspases. These aldehydes display a wide range of selectivities and potencies against these enzymes, with dissociation constants ranging from 75 pM to >10 microM. The halomethyl ketone benzyloxycarbonyl-VAD fluoromethyl ketone is a broad specificity irreversible caspase inhibitor, with second-order inactivation rates that range from 2.9 x 10(2) M-1 s-1 for caspase-2 to 2.8 x 10(5) M-1 s-1 for caspase-1. The results obtained with peptide-based inhibitors are in accord with those predicted from the substrate specificity studies described earlier. The cowpox serpin CrmA is a potent (Ki < 20 nM) and selective inhibitor of Group I caspases (caspase-1, -4, and -5) and most Group III caspases (caspase-8, -9, and -10), suggesting that this virus facilitates infection through inhibition of both apoptosis and the host inflammatory response. [1]

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Objectives: The aim of this study was to investigate whether the caspase-3 inhibitor Ac-DEVD-CHO functionally improves stunned myocardium. Background: Degradation of troponin I contributes to the pathogenesis of myocardial stunning, whereas the role of apoptosis is unknown. Caspase-3 is an essential apoptotic protease that is specifically inhibited by Ac-DEVD-CHO. Methods: Isolated working hearts of rats were exposed to 30 min of low-flow ischemia, followed by 30 min of reperfusion. Ac-DEVD-CHO (0.1 to 1 micromol/l) was added 15 min before ischemia/reperfusion or 5 min before reperfusion. Cardiac output, external heart power, left ventricular (LV) developing pressure and contractility (dp/dt(max)) were measured. Apoptosis was assessed by TUNEL staining and internucleosomal deoxyribonucleic acid fragmentation. Caspase-3 processing and troponin I cleavage were determined by immunoblotting. Caspase-3 activity was measured using a fluorogenic substrate. Results: The addition of Ac-DEVD-CHO before ischemia/reperfusion or before reperfusion dose-dependently and significantly (p < 0.05) improved post-ischemic recovery of cardiac output, external heart power, LV developing pressure and dp/dt(max), compared with the vehicle (0.01% dimethyl sulfoxide). Ac-DEVD-CHO was similarly effective when given before reperfusion. Ac-DEVD-CHO blocked ischemia/reperfusion-induced caspase-3 activation, but cardiomyocyte apoptosis was unaffected. Troponin I cleavage was not inhibited by Ac-DEVD-CHO. Conclusions: Caspase-3 is activated in stunned myocardium. Inhibition of caspase-3 by Ac-DEVD-CHO significantly improves post-ischemic contractile recovery of stunned myocardium, even when given after the onset of ischemia. The mechanism(s) of protection by Ac-DEVD-CHO appear to be independent of apoptosis. Inhibition of caspase-3 is a novel therapeutic strategy to improve functional recovery of stunned myocardium.[2]

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The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the activation of caspase-9 during apoptosis. By using a large panel of genetically modified murine embryonic fibroblasts, we show here that, in response to tumor necrosis factor (TNF), caspase-8 cleaves and activates caspase-9 in an apoptosome-independent manner. Interestingly, caspase-8-cleaved caspase-9 induced lysosomal membrane permeabilization but failed to activate the effector caspases whereas apoptosome-dependent activation of caspase-9 could trigger both events. Consistent with the ability of TNF to activate the intrinsic apoptosis pathway and the caspase-9-dependent lysosomal cell death pathway in parallel, their individual inhibition conferred only a modest delay in TNF-induced cell death whereas simultaneous inhibition of both pathways was required to achieve protection comparable to that observed in caspase-9-deficient cells. Taken together, the findings indicate that caspase-9 plays a dual role in cell death signaling, as an activator of effector caspases and lysosomal membrane permeabilization.[3]

C20H30N4O11

502.47

502.191

C, 47.81; H, 6.02; N, 11.15; O, 35.02

169332-60-9

644345

N-Acetyl-Asp-Glu-Val-Asp-al; Ac-Asp-Glu-Val-Asp-al; N-acetyl-L-alpha-aspartyl-L-alpha-glutamyl-L-valyl-L-aspart-1-al

Ac-DEVD-al

White to off-white solid powder

1.374g/cm3

1021.1ºC at 760mmHg

571.3ºC

0mmHg at 25°C

1.535

-2.6

245.37

7

11

16

35

843

4

O=C([C@]([H])(C([H])([H])C([H])([H])C(=O)O[H])N([H])C([C@]([H])(C([H])([H])C(=O)O[H])N([H])C(C([H])([H])[H])=O)=O)N([H])[C@]([H])(C(N([H])[C@]([H])(C([H])=O)C([H])([H])C(=O)O[H])=O)C([H])(C([H])([H])[H])C([H])([H])[H]

UMBVAPCONCILTL-MRHIQRDNSA-N

InChI=1S/C20H30N4O11/c1-9(2)17(20(35)22-11(8-25)6-15(29)30)24-18(33)12(4-5-14(27)28)23-19(34)13(7-16(31)32)21-10(3)26/h8-9,11-13,17H,4-7H2,1-3H3,(H,21,26)(H,22,35)(H,23,34)(H,24,33)(H,27,28)(H,29,30)(H,31,32)/t11-,12-,13-,17-/m0/s1

(4S)-4-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-carboxy-3-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: 如何溶解多肽产品？请参考本产品网页右上角“产品说明书“文件，第4页。

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配方 1 中的溶解度: 100 mg/mL (199.02 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。