Z-YVAD-FMK is a cell-permeable, irreversible inhibitor of caspase‑1 and caspase‑4 [1]. Z‑YVAD‑FMK covalently binds to and blocks the activity of caspase‑1 and caspase‑4, inhibiting the maturation and release of downstream proinflammatory cytokines such as IL‑1β and IL‑18 [2-3]. Z‑YVAD‑FMK is commonly used to study inflammation and programmed cell death [4].
In Caco-2 cells, Inactivation of caspase-1 by Z-YVAD-FMK (100μM; 48h) abolishes butyrate-induced apoptosis [5]. In bone marrow-derived macrophages (BMDMs), Z-YVAD-FMK (100μM; 30min) treatment significantly reduced the percentage of propidium iodide-positive BMDMs, the release of lactate dehydrogenase, and IL-1β [6].
In ApoE−/− mice, the area of atherosclerotic lesions in aortic sections of mice treated with Z-YVAD-FMK (6.2mg/kg; ip; 4 weeks) was reduced by approximately 49.01% [6].
References:
[1]. Katsikis P D, Garcia-Ojeda M E, Torres-Roca J F, et al. Interleukin-1β converting enzyme–like protease involvement in Fas-induced and activation-induced peripheral blood T cell apoptosis in HIV infection. TNF-related apoptosis-inducing ligand can mediate activation-induced T cell death in HIV infection[J]. The Journal of experimental medicine, 1997, 186(8): 1365-1372.
[2]. Li H, Nookala S, Re F. Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1β and IL-18 release[J]. The Journal of Immunology, 2007, 178(8): 5271-5276.
[3]. Bian Z M, Elner S G, Elner V M. Dual involvement of caspase-4 in inflammatory and ER stress-induced apoptotic responses in human retinal pigment epithelial cells[J]. Investigative ophthalmology & visual science, 2009, 50(12): 6006-6014.
[4]. Liu W, Yang D, Shi J, et al. Caspase-1 inhibitor reduces pyroptosis induced by brain death in kidney[J]. Frontiers in Surgery, 2021, 8: 760989.
[5]. Avivi-Green C, Polak-Charcon S, Madar Z, et al. Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines[J]. The Journal of nutrition, 2002, 132(7): 1812-1818.
[6]. Zhang B L, Yu P, Su E Y, et al. Inhibition of GSDMD activation by Z-LLSD-FMK or Z-YVAD-FMK reduces vascular inflammation and atherosclerotic lesion development in ApoE−/− mice[J]. Frontiers in Pharmacology, 2023, 14: 1184588.
Z-YVAD-FMK是一种可穿透细胞的不可逆caspase-1和caspase-4 抑制剂 [1]。Z-YVAD-FMK与caspase-1和caspase-4共价结合并阻断其活性，从而抑制下游促炎细胞因子（如IL-1β和IL-18）的成熟和释放 [2-3]。Z-YVAD-FMK 常用于研究炎症和程序性细胞死亡 [4]。
在Caco-2细胞中，Z-YVAD-FMK（100μM；48h）抑制caspase-1可消除丁酸诱导的细胞凋亡 [5]。在骨髓来源的巨噬细胞（BMDM）中，Z-YVAD-FMK（100μM；30min）治疗显著降低了碘化丙啶阳性BMDM的百分比、乳酸脱氢酶和IL-1β的释放 [6]。
在ApoE-/-小鼠中，接受Z-YVAD-FMK（6.2mg/kg；ip；4周）治疗的小鼠主动脉切片中动脉粥样硬化病变面积减少了约49.01% [6]。