Protein kinases play a pivotal role in cell signalling and disease and have emerged as a major drug target. Since the approval of the first small molecule inhibitor, imatinib, in 2001 more than 20 kinase inhibitors or antibodies have been approved as drugs. However, much of the human kinome remains unexplored suggesting further opportunities to address unmet medical needs in cancer, metabolism, inflammation and other human diseases. To validate these novel targets and to address their biology, highly selective chemical probes are desired. This presents a tremendous challenge due to the high sequence conservation of the kinase catalytic domains.
The SGC is therefore performing systematic screening of the human and malarial kinomes against a focussed panel of small molecule inhibitors. Large scale structural comparisons are used to understand the mechanisms of inhibitor cross reactivity and to facilitate the design of highly selective molecules. The results are released into the public domain without restrictions on use. The SGC and its collaborators have published a number of kinase chemical probes that can be found here.