Activity-based chemoproteomic profiling reveals the active kinome of Leishmania

This study provides the first ABPP survey of the <i>Leishmania</i> kinome, revealing multiple ligandable, active kinases that drive parasite survival and virulence. Our chemoproteomic approach highlights both essential protein kinases and unique metabolic kinases as a rich source of potential drug targets. These findings demonstrate that ABPP can unveil the biochemically active kinases in <i>Leishmania</i>, offering a new strategy for prioritizing kinase targets and accelerating kinase inhibitor development against leishmaniasis. The work lays a foundation for next-generation antileishmanial therapies directed at the parasite kinome, particularly those kinases indispensable for the parasite yet sufficiently divergent from the human host.