Mitogen-activated protein kinase kinase 4 (MKK4) as a promising therapeutic target in liver diseases: a review

The liver is essential for metabolism and detoxification and can regenerate effectively. However, severe injuries or major surgeries can hinder this ability, leading to liver insufficiency or failure. Recent research has identified mitogen-activated protein kinase kinase 4 (MKK4) as a key negative regulator of liver regeneration, making it a promising therapeutic target. Inhibiting MKK4 reduces apoptosis and enhances liver regeneration, spurring interest in small molecule inhibitors of MKK4 for therapeutic strategies to promote liver recovery. This review systematically elucidates the structural characteristics and biological functions of MKK4, alongside its regulatory mechanisms in liver regeneration. It emphasises recent advancements in the research of small molecule inhibitors targeting MKK4 and offers a thorough and comprehensive analysis of the structure-activity relationships of the reported MKK4 inhibitors. The objective is to provide theoretical insights and research directions for the development of efficient and specific MKK4 inhibitors.