The kinase MKK4 is a regulator of hepatocyte regeneration. A new study published in Cell reports the development of small-molecule inhibitors of MKK4. HRX215 increased liver regeneration post-hepatectomy in mouse and pig models and increased hepatocyte proliferation in fibrotic mouse livers post-partial hepatectomy. In addition, HRX215 treatment prevented post-hepatectomy liver failure in a lethal 85% hepatectomy model in pigs and enabled their survival. Next, a phase I trial (EudraCT 2021-000193-28; n = 48 healthy volunteers) of HRX215 demonstrated positive safety and pharmacokinetics.

中文翻译：

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用于肝再生的 MKK4 抑制剂的开发

激酶 MKK4 是肝细胞再生的调节因子。发表在《Cell》上的一项新研究报告了 MKK4 小分子抑制剂的开发。 HRX215 增加小鼠和猪模型肝切除后的肝脏再生，并增加部分肝切除后纤维化小鼠肝脏的肝细胞增殖。此外，HRX215治疗在猪的致死性85%肝切除模型中预防了肝切除后肝衰竭，并使其得以生存。接下来，HRX215 的 I 期试验（EudraCT 2021-000193-28；n  = 48 名健康志愿者）证明了积极的安全性和药代动力学。