Q-VD-OPh hydrate is a broad-spectrum, cell-permeable, highly potent and non-toxic caspase inhibitor, with IC50 values ranging from 25 to 400nM for recombinant caspase-1, -3, -8, and -9[1]. Q-VD-OPh hydrate significantly inhibits actinomycin D-induced apoptosis and demonstrates superior efficacy in preventing cell death compared to the widely used inhibitors Z-VAD-FMK and Boc-D-FMK[2], and is commonly applied in apoptosis mechanism research, cytoprotection, and in vitro biochemical assays of caspase activity[3,4].
In vitro, pretreatment of mouse WEHI 231 cells with Q-VD-OPh hydrate (1-100μM) for 1h significantly reduces actinomycin D (1μg/mL; 4h)-induced apoptosis. While actinomycin D alone induces apoptosis in 92% of cells within 4h, pretreatment with 1μM and 2.5μM Q-VD-OPh hydrate reduces apoptosis by 22% and 48%, respectively. Complete protection of WEHI 231 cells is achieved at concentrations ranging from 5 to 100μM[2]. Treatment of human neutrophils with 10μM Q-VD-OPh hydrate for 5 days demonstrates that the compound maintains cell viability and function for at least 5 days, indicating that a single 10μM dose is sufficient to significantly extend cellular lifespan[5].
In vivo, administration of Q-VD-OPh hydrate (10mg/kg) via intraperitoneal injection in neonatal mice with hypoxia-ischemia (HI) injury, even when delayed until 12 and 36h post-HI, effectively suppressed caspase-3 activity in ischemic brain tissue and reduced the expression of pro-inflammatory cytokines CCL2 and CCL3 at 48h after HI[6]. In a rat model of spinal cord injury (SCI), treatment with Q-VD-OPh hydrate (0.4mg/kg) via intraperitoneal injection immediately after injury and again at 24h significantly decreases the number of apoptotic cells in spinal tissue and results in less severe pathological damage compared to the control group (including hemorrhage, edema, and necrosis)[7].
References:
[1] ROHN T T, KOKOULINA P, EATON C R, et al. Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh[J]. International journal of clinical and experimental medicine, 2009, 2(4): 300.
[2] CASERTA T M, SMITH A N, GULTICE A D, et al. Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties[J]. Apoptosis, 2003, 8(4): 345-352.
[3] BROWN T L. Q-VD-OPh, next generation caspase inhibitor[M]//Cell Volume and Signaling. Boston, MA: Springer US, 2004: 293-300.
[4] RENOLLEAU S, FAU S, GOYENVALLE C, et al. Specific caspase inhibitor Q-VD-OPh prevents neonatal stroke in P7 rat: a role for gender[J]. Journal of neurochemistry, 2007, 100(4): 1062-1071.
[5] KHUU L, PILLAY A, PRICHARD A, et al. Effects of the pan-caspase inhibitor Q-VD-OPh on human neutrophil lifespan and function[J]. PloS one, 2025, 20(1): e0316912.
[6] HAN W, SUN Y, WANG X, et al. Delayed, long-term administration of the caspase inhibitor Q-VD-OPh reduced brain injury induced by neonatal hypoxia-ischemia[J]. Developmental neuroscience, 2014, 36(1): 64-72.
[7] ANTAR V, AKDEMIR O, SAĞMANLIGIL A, et al. Q-VD-OPh, a pancaspase inhibitor, reduces trauma-induced apoptosis and improves the recovery of hind-limb function in rats after spinal cord injury[J]. Neurocirugia, 2009, 20(6): 533-540.
Q-VD-OPh hydrate是一种广谱、可渗透细胞、高效且无毒的caspase抑制剂，对重组caspase1,3,8和9的IC50值在25-400nM范围内[1]。Q-VD-OPh hydrate可显著抑制actinomycin D诱导的细胞凋亡，且在预防细胞死亡方面明显优于广泛使用的抑制剂ZVAD-fmk和Boc-D-fmk[2]，故常用于细胞凋亡机制、细胞保护和caspase的体外生化分析等研究[3,4]。
在体外，Q-VD-OPh hydrate（1-100μM）预处理小鼠WEHI 231细胞1h，可显著减少由actinomycin D（1μg/mL; 4h）诱导引起的细胞凋亡。单独的actinomycin D在4h内会诱导92%的细胞凋亡，而1μM Q-VD-OPh hydrate可将细胞凋亡减少22%，2.5μM Q-VD-OPh hydrate可将细胞凋亡减少48%，5-100μM Q-VD-OPh hydrate可完全保护WEHI 231细胞[2]。Q-VD-OPh hydrate（10μM）处理人类中性粒细胞5天，结果表明其可维持人类中性粒细胞的活力和功能至少5天，故单次10μM剂量的该药物足以显著延长细胞的寿命[5]。
在体内，Q-VD-OPh hydrate（10mg/kg）通过腹腔注射治疗缺氧缺血的HI（hypoxia-ischemia）新生小鼠，分别在HI损伤后12h和36h延迟给药，于HI后48h后发现该处理能有效抑制缺血脑组织中caspase-3的活性并减少促炎因子CCL2和CCL3的表达[6]。Q-VD-OPh hydrate (0.4mg/kg)通过腹腔注射治疗创伤性脊髓损伤的Wistar大鼠，于损伤后立即首次给药并在24h后再次给药，显著降低了脊髓组织中凋亡细胞的数量，并较对照组表现出更轻的病理损伤（包括出血，水肿和坏死）[7]。