Advances of small molecule targeting of kinases

Norbert Berndt, Rezaul M Karim, Ernst Schönbrunn

Current Opinion in Chemical Biology
Volume 39, August 2017, Pages 126–132

doi: 10.1016/j.cbpa.2017.06.015

Reversible protein phosphorylation regulates virtually all aspects of life in the cell. As a result, dysregulation of protein kinases, the enzymes responsible for transferring phosphate groups from ATP to proteins, are often the cause or consequence of many human diseases including cancer. Almost three dozen protein kinase inhibitors (PKIs) have been approved for clinical applications since 1995, the vast majority of them for the treatment of cancer. According to the NCI, there are more than 100 types of cancer. However, FDA-approved PKIs only target 14 of them. Importantly, of the more than 500 protein kinases encoded by the human genome, only 22 are targets for currently approved PKIs, suggesting that the reservoir of PKIs still has room to grow significantly. In this short review we will discuss the most recent advances, challenges, and alternatives to currently adopted strategies in this burgeoning field.