Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer

A novel 5-phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione series of MEK inhibitors has been developed using structure-based drug design. Lead optimization of this series led to the discovery of TAK-733. This was advanced to Phase I clinical studies for cancer treatment.

Graphical abstractA series of potent 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione inhibitors of MEK kinase was designed and synthesized. Structural properties and biological activities are described.Figure optionsDownload full-size imageDownload as PowerPoint slide