molecules of the month

The BMS AAK1 kinase inhibitor, compound 59, is brain-penetrant and acts on the CNS. The target was identified from a phenotypic screen of mouse knockouts, and a non-brain penetrant inhibitor doesn’t show in vivo activity, confirming the central activity needed on the target. Targeting a kinase in the CNS for pain is bold due to the high bar for safety required, but recent advances in achieving selectivity with kinase inhibitors for broader therapeutic areas such as inflammation makes it seem achievable. As Jake points out, an increasing number of kinase inhibitors are entering the clinic for non-cancer CNS indications such as for LRRK2, DLK, and RIPK1.