Cyclin dependent protein kinases (CDKs) have become attractive drug targets in an effort toidentify effective inhibitors of the parasite Plasmodium falciparum, the causative agent of themost severe form of human malaria. We tested known CDK inhibitors for their ability to inhibittwo malarial CDKs: Pfmrk and PfPK5. Many broad spectrum CDK inhibitors failed to inhibitPfmrk suggesting that the active site differs from other CDKs in important ways. By screeningcompounds in the Walter Reed chemical database, we identified oxindole-based compounds aseffective inhibitors of Pfmrk (IC50 = 1.5 μM). These compounds have low cross-reactivity againstPfPK5 and human CDK1 demonstrating selectivity for Pfmrk. Amino acid comparison of theactive sites of Pfmrk and PfPK5 identified unique amino acid differences that may explainthis selectivity and be exploited for further drug development efforts.
