The Hyvönen Group, together with the Spring Group from Chemistry, Apollo Therapeutics and Sandexis, have published a paper in the Journal of Medicinal Chemistry. The paper describes the discovery of APL-5125, a highly selective and potent small molecule CK2a inhibitor.
This ground-breaking collaboration resulted from a serendipitous finding by the Hyvönen Group’s Paul Brear of a cryptic αD pocket in CK2α. Together with David Spring’s Group in the Yusuf Hamied Department of Chemistry they then demonstrated, with the development of CAM4066 inhibitor, the αD pocket’s use as a specificity-driving site for a novel class of ATP-competitive CK2α inhibitors.
With this proof-of-concept work at hand, the project was taken on by Apollo Therapeutics with an aim of developing a specific and efficacious CK2α inhibitor for the treatment of cancers.
The long and exciting journey from discovery to potential therapeutic impact is now complete with APL-5125 currently being evaluated in a Phase 1/2 clinical trial in the United States in patients with solid tumours, including metastatic colorectal carcinoma.
Read the paper: ‘Exploiting the Cryptic αD Pocket of Casein Kinase 2α (CK2α) to Deliver Highly Potent and Selective Type 1 Inhibitors’.