Wee1 kinase inhibitor IMP7068

An orally bioavailable inhibitor of the human tyrosine kinase Wee1 (Wee1-like protein kinase; Wee1A kinase; WEE1hu), with potential antineoplastic activity. Upon oral administration, Wee1 kinase inhibitor IMP7068 targets, binds to and inhibits Wee1. Inhibition of Wee1 inhibits Cdk1 (Cdc2) phosphorylation, promotes both premature mitosis and a prolonged mitotic arrest, which results in the accumulation of unrepaired DNA damage. This leads to apoptosis in susceptible tumor cells, such as p53-deficient or mutated human cancers that lack the G1 checkpoint. Unlike normal cells, most p53-deficient or mutated human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Overexpression of Wee1 occurs in several cancer types and high expression of Wee1 is associated with poor outcomes. Wee1 phosphorylates Cdc2 in the Cdc2/cyclin B (CDK1/cyclin B) complex which blocks progression from G2 into mitosis. The Wee1 tyrosine kinase is activated upon DNA damage and regulates the G2-M and S cell cycle checkpoints.