darizmetinib

Darizmetinib (HRX-0215) is a first-in-class, orally active small molecule inhibitor of mitogen-activated protein kinase kinase 4 (MKK4), also known as MAP2K4 or MEK4. It is being developed by HepaRegeniX for the treatment of acute and chronic liver diseases. By selectively inhibiting MKK4, darizmetinib enhances the MKK7 and JNK1 signaling pathways, leading to activation of transcription factors such as ATF2 and ELK1. This mechanism promotes hepatocyte proliferation and liver regeneration while protecting hepatocytes from cell death in models of acute liver injury. Preclinical studies demonstrated efficacy in boosting liver regeneration after partial hepatectomy without affecting intact livers. Phase 1 clinical trials showed that darizmetinib was safe and well tolerated in healthy volunteers[1][2][3][8].