Sarcocystis neurona (Sn) CDPK1 has an atypical small gatekeeper residue selectively inhibited by BKIs. Evidence is provided that shows SnCDPK1 is a potential target for rational EPM drug development. Bumped kinase inhibitors interfered with an early step in S. neurona tachyzoite host cell invasion. Nine of 10 mice in a BKI-1553 experimentally treated group were cured of equine protozoal myeloencephalitis.