Scaffold-based design of kinase inhibitors for cancer therapy

Kinase inhibitors have already established a foothold in the current armament for the treatment of malignancies. Indeed, the future of cancer therapy is likely to rely heavily on an ever-growing number of kinase inhibitors, either as single-agents or in combination with other targeted drugs or even chemotherapies. The progress of the past decade has been driven increasingly by improvements in an integrated drug discovery paradigm that starts with smaller molecular starting points, termed scaffolds, and incorporates X-ray crystallography at the outset of the project. Guided throughout by structural information, the medicinal chemistry efforts are streamlined and enhanced. Here, we review such a paradigm termed scaffold-based design and show how implementation of these methods results in novel, potent, and specific drug candidates.