Z-DEVD-FMK

Z-DEVD-FMK is a specific irreversible cysteine-aspartic protease 3 (caspase-3) inhibitor with an IC₅₀ of 18μM^[1]. Z-DEVD-FMK is commonly used to study apoptosis and neuroprotection ^[2].

In vitro, Z-DEVD-FMK (50μM) treated cardiomyocytes for 24h, significantly reduced ceramide-induced apoptosis and increased cell survival rate to 81% ^[3]. Z-DEVD-FMK (15μM) can effectively reduce caspase-3 activity when treating renal proximal tubular cells, but the effect of reducing cell apoptosis is not as good as that of pan-caspase inhibitors ^[4].

In vivo, Z-DEVD-FMK (160 ng) treated mice with traumatic brain injury (TBI) via intracerebroventricular injection, reduced the lesion volume after central nervous system injury, and improved motor and cognitive functions ^[2]. Z-DEVD-FMK (20 mg/kg) treated diabetic mice via intraperitoneal injection for 8 weeks, which improved proteinuria, renal function, and tubulointerstitial fibrosis in mice, and slowed down the decrease in serum albumin levels ^[5] . Z-DEVD-FMK (0.2 mg/kg) is injected into the eyeball to treat optic nerve injury in rabbits, significantly reducing the apoptosis of retinal ganglion cells and promoting the recovery of optic nerve function ^[6].

References:
[1] Kanthasamy A G, Anantharam V, Zhang D, et al. A novel peptide inhibitor targeted to caspase-3 cleavage site of a proapoptotic kinase protein kinase C delta (PKCδ) protects against dopaminergic neuronal degeneration in Parkinson’s disease models[J]. Free Radical Biology and Medicine, 2006, 41(10): 1578-1589.
[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[J]. Journal of Cerebral Blood Flow & Metabolism, 2004, 24(10): 1119-1132.
[3] Wang J, Zhen L, Klug M G, et al. Involvement of caspase 3-and 8-like proteases in ceramide-induced apoptosis of cardiomyocytes[J]. Journal of cardiac failure, 2000, 6(3): 243-249.
[4] Yang B, El Nahas A M, Fisher M, et al. Inhibitors directed towards caspase-1 and-3 are less effective than pan caspase inhibition in preventing renal proximal tubular cell apoptosis[J]. Nephron Experimental Nephrology, 2004, 96(2): e39-e51.
[5] Wen S, Wang Z H, Zhang C X, et al. Caspase-3 promotes diabetic kidney disease through gasdermin E-mediated progression to secondary necrosis during apoptosis[J]. Diabetes, Metabolic Syndrome and Obesity, 2020: 313-323.
[6] Zhang W, Yu J G, Wang X, et al. Experimental study on treatment of rabbits optic nerve injury with Caspase-3 inhibitor z-DEVD-fmk[J]. [Zhonghua yan ke za Zhi] Chinese Journal of Ophthalmology, 2010, 46(12): 1084-1089.

Z-DEVD-FMK是一种特异性的不可逆的半胱氨酸-天冬氨酸蛋白酶3（caspase-3）抑制剂，IC₅₀为18μM^[1]。Z-DEVD-FMK通常用于研究细胞凋亡和神经保护^[2]。

在体外，Z-DEVD-FMK（50μM）处理心肌细胞24h，显著减少神经酰胺诱导的细胞凋亡，将细胞存活率提高至 81%^[3]。Z-DEVD-FMK（15μM）处理肾近端肾小管细胞，可有效降低caspase-3活性，但是减少细胞凋亡的效果不如泛半胱天冬酶抑制剂^[4]。

在体内，Z-DEVD-FMK（160 ng）通过脑室内注射治疗创伤性脑损伤（TBI）小鼠，可减少中枢神经系统损伤后的病变体积，改善了运动和认知功能^[2]。Z-DEVD-FMK（20mg/kg）通过腹膜注射治疗糖尿病小鼠8周，改善了小鼠的蛋白尿、肾功能和肾小管间质纤维化，并减缓了血清白蛋白水平的下降^[5]。Z-DEVD-FMK（0.2mg/kg）通过眼球注射治疗视神经损伤兔子，显著降低视网膜神经节细胞的凋亡，并促进视神经功能的恢复^[6]。