How many kinases are druggable? A review of our current understanding.

ABSTRACT

There are over 500 human kinases ranging from very well-studied to almost completely ignored. Kinases are tractable and implicated in many diseases, making them ideal targets for medicinal chemistry campaigns, but is it possible to discover a drug for each individual kinase? For every human kinase, we gathered data on their citation count, availability of chemical probes, approved and investigational drugs, PDB structures, and biochemical and cellular assays. Analysis of these factors highlights which kinase groups have a wealth of information available, and which groups still have room for progress. The data suggest a disproportionate focus on the more well characterized kinases while much of the kinome remains comparatively understudied. It is noteworthy that tool compounds for understudied kinases have already been developed, and there is still untapped potential for further development in this chemical space. Finally, this review discusses many of the different strategies employed to generate selectivity between kinases. Given the large volume of information available and the progress made over the past 20 years when it comes to drugging kinases, we believe it is possible to develop a tool compound for every human kinase. We hope this review will prove to be both a useful resource as well as inspire the discovery of a tool for every kinase.