greatwall kinase inhibitor

Greatwall kinase inhibitor (GWLi) refers to a novel small molecule therapeutic developed by the Hochegger lab at the University of Sussex, designed to target the Greatwall kinase (GWL), also known as microtubule-associated serine/threonine kinase-like (MASTL). GWL is a critical regulator of mitosis that functions by phosphorylating Arpp19 and ENSA, which subsequently bind to and inhibit the protein phosphatase 2A-B55 (PP2A-B55) complex. This inhibition stabilizes mitotic Cdk1-dependent phosphorylation sites, facilitating cell cycle progression. By blocking GWL activity, the inhibitor prevents the inactivation of PP2A-B55, leading to G2/M phase cell cycle arrest and the induction of apoptosis. Preclinical research has demonstrated the potential of GWLi in treating hematological malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), where it has shown efficacy in reducing cell cycling and inducing apoptosis, as well as potential synergy with BCL2 inhibitors like venetoclax.

Other names

MASTL inhibitorGWL inhibitor