Ac-DEVD-CHO|169332-60-9|安捷凯

Ac-DEVD-CHO

Ac-DEVD-CHO (Caspase-3 Inhibitor I, N-Ac-Asp-Glu-Val-Asp-CHO) is a potent aldehyde inhibitor of Group II caspases with Ki values of 0.2 nM and 0.3 nM for for caspase-3 and caspase-7, respectively. Weak inhibition for caspase-2.

此产品仅用于科学研究，我们不为任何个人用途提供产品和服务

Background

Ac-DEVD-CHO is a potent inhibitor of caspase-3 (Ki = 230 pM). In contrast, caspase-2 cleaves the tetrapeptide substrate poorly and is only weakly inhibited by this aldehyde (Ki = 1.7 μM). Group III caspases are broadly inhibited by Ac-DEVD-CHO with Ki values ranging from 1 to 300 nM[1]. Inhibition of caspase-3 by Ac-DEVD-CHO in isolated working-heart rat model 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. Troponin I cleavage was not inhibited by Ac-DEVD-CHO[2].

Ac-DEVD-CHO administered at the time of MI results in a 61% reduction in activated caspase-3 expression in cardiomyocytes (p<0.05), and an 84% reduction in cardiomyocyte apoptosis in the young animals. However, in the aging mice, caspase inhibition had no effect on activated caspase-3 expression or cardiomyocyte apoptosis[4]. Ac-DEVD-CHO suppressed and/or delayed the progression of photoreceptor cell damage in rats and delays disease progression in rd gene-carring mice, which normally develop retinal degeneration early in life[2].

[1] Garcia-Calvo M, et al. J Biol Chem. 1998, 273(49):32608-13. [2] Ruetten H, et al. J Am Coll Cardiol. 2001, 38(7):2063-70. [3] Gyrd-Hansen M, et al. Mol Cell Biol. 2006, 26(21):7880-91.

Protocol

Cell experiment:

OCLs are incubated with RANKL and treated with 0.5 mM SIN with or without the specific caspase-3 inhibitor Ac-DEVD-CHO (10 μM) for 24 h. At the end of the treatment, the cells are washed with PBS and are stained for 15 min with 10 μM Hoechst 33258 dye. Images of the staineing cells are captured with a fluorescent microscope. The differences are evaluated by counting the number of cells with apoptotic nuclear condensation in each well[4].

Animal experiment:

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].

参考文献:

[1]. Garcia-Calvo M, et al.nhibition of human caspases by peptide-based and macromolecular inhibitors. J Biol Chem. 1998 Dec 4;273(49):32608-13.
[2]. Jinglin Wang, et al. A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice. Oncotarget. 2017 Jan 3; 8(1): 610-623.
[3]. Junping Zhang, et al. Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro. Cancer Cell Int. 2015; 15: 58
[4]. Long-gang He, et al. Sinomenine induces apoptosis in RAW 264.7 cell-derived osteoclasts in vitro via caspase-3 activation. Acta Pharmacol Sin. 2014 Feb; 35(2): 203-210.
[5]. Liu LX, et al. The effect of caspase-3 inhibitor on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection in mice. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010 Dec;22(12):736-9.

安捷凯在线客服

扫一扫加微信

信号通路

生命科学

有机化学

无机化学

材料科学

Ac-DEVD-CHO

Ac-DEVD-CHO详情

Background

Protocol

安捷凯在线客服