Ac-DEVD-CMK is a cell-permeable and irreversible caspase-3 inhibitor [1][2][3].
Apoptosis is a process of programmed cell death that occurs in multicellular organisms. Caspase are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis, pyroptosis and necroptosis) and inflammation. Caspase activation is a major event in apoptosis. Caspase-3 cleaves and activates caspases 6 and 7, and is processed and activated by caspases 8, 9, and 10 [1][2][3].
Ac-DEVD-CMK (Ac-Asp-Glu-Val-Asp-CH2Cl) is a cell-permeable, irreversible and specific caspase-3 inhibitor. In coronary occlusion/reperfusion rat isolated hearts, Ac-DEVD-CMK reduced infarct size (the percentage of infarction 27.8+3.3% vs control 38.5+2.6%), suggesting that caspase inhibition during early reperfusion protected myocardium against lethal reperfusion injury [1]. In BL41 cells, Ac-DEVD-CMK partially inhibited Mn2+-induced apoptosis and PARP cleavage, and partially blocked B cell death by 37% even at 100 μM [2]. Ac-DEVD-CMK significantly blocked neurotoxicity at 24 hr after 1 hr of SIN-1 exposure and also protected against neurotoxicity at 24 hr after 90 min of zinc (75 μM) exposure. Ac-DEVD-CMK completely blocked SIN-1-induced activation of caspase-3 [3].
References:
[1]. Mocanu MM, Baxter GF, Yellon DM. Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury. Br J Pharmacol. 2000 May;130(2):197-200.
[2]. Schrantz N, Blanchard DA, Mitenne F, et al. Manganese induces apoptosis of human B cells: caspase-dependent cell death blocked by bcl-2. Cell Death Differ. 1999 May;6(5):445-53.
[3]. Zhang Y, Wang H, Li J, et al. Peroxynitrite-induced neuronal apoptosis is mediated by intracellular zinc release and 12-lipoxygenase activation. J Neurosci. 2004 Nov 24;24(47):10616-27.