darizmetinib

An orally bioavailable inhibitor of mitogen-activated protein (MAP) kinase kinase 4 (MKK4; MAP2K4), with potential hepatoprotective, proliferative, and hepato-regenerative activities. Upon oral administration, darizmetinib selectively targets, binds to and inhibits the activity of MKK4 in liver cells. This allows for signaling through MKK7 and mitogen-activated protein kinase 8 (MAPK8; stress-activated protein kinase 1; JNK-1) proliferation-enhancing pathways, thereby activating the transcription factors activating transcription factor 2 (ATF2) and ETS domain-containing protein ELK1. This promotes hepatocyte proliferation, increases hepatocyte survival and liver regeneration upon hepatectomy. This may prevent liver failure, restore liver mass, and may protect hepatocytes from cell death. MKK4, a MAP2K and part of the stress-activated protein kinase (SAPK)/mitogen-activated protein kinase (MAPK) signaling pathways, plays a key role in preventing cellular proliferation and the regulation of hepatocyte regeneration. Suppression of MKK4 promotes the regenerative capacity of hepatocytes.