Emricasan is an orally active, irreversible, broad-spectrum caspase inhibitor with good pharmacokinetic profile [1]. Emricasan inhibits Zika virus (ZIKV) infection and suppresses infection-induced caspase-3 activity, leading a reduction in cell death[2]. Emricasan has been widely used in mouse models of liver injury to inhibit liver fibrosis and restore liver function[3].
In vitro, Emricasan treatment for 72h significantly inhibited the cell death induced by the ZIKV virus strains FSS13025 and PRVABC59 in the SNB-19 cells, with IC50 values of 0.84μM and 0.45μM, respectively[4]. Treatment with 10μM Emricasan for 72 hours significantly inhibited the cytotoxicity of HEI-OC1 cells induced by cisplatin[5]. Pre-treatment with 5μM Emricasan for 30 minutes can enhance the cell-killing effect of birinapant on MLL-AF9 cells and increase the expression of TNF[6].
In vivo, Emricasan treatment via oral administration at a dose of 10mg/kg/day for 7 consecutive days significantly inhibited hepatocyte death in late-stage liver cirrhosis rats and improved liver function, alleviating portal hypertension and liver microvascular dysfunction[7]. Intragastric administration of Emricasan at a single dose of 15mg/kg 15 minutes before ischemia alleviated cerebral IS/reperfusion injury in rats and reduced the infarct area[8].
References:
[1] Lekakis V, Cholongitas E. The impact of emricasan on chronic liver diseases: current data[J]. Clinical Journal of Gastroenterology, 2022, 15(2): 271-285.
[2] Da Silva S, Oliveira Silva Martins D, Jardim A C G. A review of the ongoing research on Zika virus treatment[J]. Viruses, 2018, 10(5): 255.
[3] Lekakis V, Cholongitas E. The impact of emricasan on chronic liver diseases: current data[J]. Clinical Journal of Gastroenterology, 2022, 15(2): 271-285.
[4] Xu M, Lee E M, Wen Z, et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen[J]. Nature medicine, 2016, 22(10): 1101-1107.
[5] Nassauer L, Schott J W, Harre J, et al. The caspase-inhibitor Emricasan efficiently counteracts cisplatin-and neomycin-induced cytotoxicity in cochlear cells[J]. Journal of Molecular Medicine, 2024, 102(9): 1163-1174.
[6] Brumatti G, Ma C, Lalaoui N, et al. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia[J]. Science translational medicine, 2016, 8(339): 339ra69-339ra69.
[7] Gracia‐Sancho J, Manicardi N, Ortega‐Ribera M, et al. Emricasan ameliorates portal hypertension and liver fibrosis in cirrhotic rats through a hepatocyte‐mediated paracrine mechanism[J]. Hepatology communications, 2019, 3(7): 987-1000.
[8] Tian J, Guo S, Chen H, et al. Combination of emricasan with ponatinib synergistically reduces ischemia/reperfusion injury in rat brain through simultaneous prevention of apoptosis and necroptosis[J]. Translational Stroke Research, 2018, 9(4): 382-392.
Emricasan是一种口服有效、不可逆的广谱胱天蛋白酶抑制剂，具有良好的药代动力学特征[1]。Emricasan抑制Zika病毒（ZIKV）感染，并抑制感染诱导的caspase-3活性，从而减少细胞死亡[2]。Emricasan已被广泛用于肝损伤小鼠模型，以抑制肝纤维化和恢复肝功能[3]。
在体外，Emricasan处理72小时显著抑制了ZIKV毒株FSS13025和PRVABC59在SNB-19细胞中诱导的细胞死亡，IC50值分别为0.84µM和0.45µM[4]。使用10µM的Emricasan处理72小时，显著抑制了顺铂诱导的HEI-OC1细胞的细胞毒性[5]。使用5µM的Emricasan预处理30分钟，可增强birinapant对MLL-AF9细胞的杀伤作用，并增加TNF的表达[6]。
在体内，每日口服给予10mg/kg剂量Emricasan，连续7天，显著抑制了晚期肝硬化大鼠的肝细胞死亡，改善了肝功能，缓解了门静脉高压和肝脏微血管功能障碍[7]。在缺血前15分钟单次灌胃给予15mg/kg剂量的Emricasan，减轻了大鼠脑缺血/再灌注损伤，并减少了梗死面积[8]。