Uses
A potent, cell-permeable, and irreversible inhibitor of caspase-3; also inhibits caspases -6, -7, -8, and -10. Commonly used at concentrations up to 100 M to examine the role of caspase-3-dependent apoptosis
Uses
Ac-DEVD-CMK is a cell-permeable, and irreversible inhibitor of caspase-3 as well as caspase-6, -7, -8, and -10. It is commonly used at concentrations up to 100 μM to examine the role of caspase-3-dependent apoptosis in biological systems.
Biological Activity
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].
in vivo
Ac-DEVD-CMK (Caspase-3 Inhibitor III; 25 mg/kg; IP; single dose; 3 hours post-APAP) significantly attenuates Acetaminophen (APAP; HY-66005)-induced liver injury (AILI)[5].
Ac-DEVD-CMK (25 mg/kg; ip; single dose) significantly attenuates APAP-induced liver injury (AILI) in susceptible Sdc1/ mice[6].
| Animal Model: | 6- to 8-week-old females and males Sdc1-/-mice[4] |
| Dosage: | 25 mg/kg |
| Administration: | IP; single dose; 3 hours post-APAP |
| Result: | Significantly attenuated APAP (ip; 500 or 625 mg/kg)-induced liver injury (AILI), indicating that inhibition of GSK-3β or caspase-3 activity mitigates liver damage. |
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.
