Cyclin dependent protein kinases (CDKs) have become attractive drug targets in 
an effort to identify effective inhibitors of the parasite Plasmodium 
falciparum, the causative agent of the most severe form of human malaria. We 
tested known CDK inhibitors for their ability to inhibit two malarial CDKs: 
Pfmrk and PfPK5. Many broad spectrum CDK inhibitors failed to inhibit Pfmrk 
suggesting that the active site differs from other CDKs in important ways. By 
screening compounds in the Walter Reed chemical database, we identified 
oxindole-based compounds as effective inhibitors of Pfmrk (IC(50) = 1.5 microM). 
These compounds have low cross-reactivity against PfPK5 and human CDK1 
demonstrating selectivity for Pfmrk. Amino acid comparison of the active sites 
of Pfmrk and PfPK5 identified unique amino acid differences that may explain 
this selectivity and be exploited for further drug development efforts.