Z-LEHD-FMK is an irreversible caspase-9 inhibitor. Z-LEHD-FMK prevents apoptosis by inhibiting caspase-9 activity and reduces neural damage by protecting neurons[1-2]. Z-LEHD-FMK can be used in research related to apoptosis and neuroprotection[3-4].
In vitro, pretreatment of HTLV-1-transformed C81 cells with Z-LEHD-FMK (100μM) for 1 hour, followed by stimulation with LY294002 (40μM) for 24-72 hours, significantly prevented LY294002-induced apoptosis[5]. Pretreatment of SGC7901 cells with Z-LEHD-FMK (20μM) for 30 minutes, followed by co-incubation with G503 (20μM) for 24 hours, reduced the rate of G503-induced apoptotic cells[6].
In vivo, a single intraperitoneal injection of Z-LEHD-FMK (3mg/kg) 2 hours before CCl₄ injection was administered to C57BL/b6N mice. Z-LEHD-FMK significantly exacerbated CCl₄-induced acute liver injury and down-regulated the expression of hepatoprotective autophagy markers[7]. A single intravenous injection of Z-LEHD-FMK (0.8μmol/kg) administered 1 minute after trauma, or continuous injection for 7 days, was used in rats that suffered thoracic spinal cord contusion. Z-LEHD-FMK effectively blocked post-traumatic apoptosis and was associated with better neurological functional recovery outcomes[8].
References:
[1] Mullani N, Singh MK, Sharma A, et al. Caspase-9 inhibitor Z-LEHD-FMK enhances the yield of in vitro produced buffalo (Bubalus bubalis) pre-implantation embryos and alters cellular stress response. Res Vet Sci. 2016 Feb;104:4-9.
[2] Ozoren N, Kim K, Burns TF, et al. The caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res. 2000 Nov 15;60(22):6259-65.
[3] Zhang J, Chen Z, Wang S, et al. Prodelphinidin from purple sweet potato induces apoptosis in human triple-negative breast cancer cells via ROS-mediated ER stress activation. Med Oncol. 2025 Mar 6;42(4):92.
[4] Kim TI, Pak JH, Tchah H, et al. Ceramide-induced apoptosis in rabbit corneal fibroblasts. Cornea. 2005 Jan;24(1):72-9.
[5] Jeong SJ, Dasgupta A, Jung KJ, et al. PI3K/AKT inhibition induces caspase-dependent apoptosis in HTLV-1-transformed cells. Virology. 2008 Jan 20;370(2):264-72.
[6] Huang L, Zhang T, Li S, et al. Anthraquinone G503 induces apoptosis in gastric cancer cells through the mitochondrial pathway. PLoS One. 2014 Sep 30;9(9):e108286.
[7] Guo R, Lin B, Pan JF, et al. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy. Sci Rep. 2016 Sep 1;6:32447.
[8] Colak A, Karaoğlan A, Barut S, et al. Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury. J Neurosurg Spine. 2005 Mar;2(3):327-34.
Z-LEHD-FMK是一种不可逆的caspase-9抑制剂。Z-LEHD-FMK可抑制caspase-9活性来防止细胞凋亡，同时通过保护神经元以减少神经损伤[1-2]。Z-LEHD-FMK可用于细胞凋亡研究和神经保护研究的相关研究[3-4]。
在体外，Z-LEHD-FMK（100μM）预处理HTLV-1转化的C81细胞1小时，随后以LY294002（40μM）刺激24-72小时，可显著防止LY294002诱导的细胞凋亡[5]。Z-LEHD-FMK（20μM）预处理SGC7901细胞30分钟，随后与G503（20μM）共同孵育24小时，可降低G503诱导的凋亡细胞率[6]。
在体内，Z-LEHD-FMK（3mg/kg）在CCl4注射前2小时单次腹腔注射，用于处理C57BL/b6N小鼠。Z-LEHD-FMK显著加剧了CCl4诱导的急性肝损伤，并下调了肝保护性自噬标志物的表达[7]。Z-LEHD-FMK（0.8μmol/kg）在创伤后1分钟单次静脉注射，或连续注射7天，用于处理遭受胸段脊髓挫伤的大鼠。Z-LEHD-FMK有效阻断了创伤后的细胞凋亡，并与更好的神经功能恢复结果相关[8]。