Oral, selective Wee1 inhibitor
Many cancer treatments such as radiation, antimetabolites, alkylating agents, DNA topoisomerase inhibitors and platinum compounds damage DNA in cells. The cellular response is to arrest the cell cycle temporarily to allow for DNA repair hence reducing the effects of chemotherapy. The WEE1 kinase is a key regulator of the G2 checkpoint and there is emerging evidence demonstrating that it also has critical functions as a regulator of the S phase and as an epigenetic modifier. These findings in conjunction with the frequently found functional inactivation of p53, which controls the G1 cell cycle arrest, means that Wee1 inhibitors may have great value across a multitude of cancer types in both combination and monotherapy modalities.
Novel Wee1 inhibitors have been designed and optimized which exhibit high potency (IC50 < 5 nM) and excellent selectivity profile over a panel of more than 50 kinases. These inhibitors demonstrate potent anti-proliferative activity in a variety of cell lines from different tissues of origin both in combination with genotoxics and as a single agent.
The Wee1 program was partnered for further development with Debiopharm International in June 2017. Find out more through our press release here.