In Vitro Screening of Validated Plasmodium Kinases

Compound Structure Targets Potency PDBs for target References 

Purfalcamine 2 jc/o HO Cuio 6-, CDPKl ICS0 = 17 nM ECso = 230 nM TG homologue Ref. 23 

Purported Kinase Inhibitors from GSK TCAMS Library, each active at 2 pM on whole parasites 

Finally, the imidazopyridazine series elaborated as inhibitors of PfPK7 in Bouloc et al.,4S was progressed from an initial 11 pM hit to the final compound (compound 4) of 131 nM. The most potent compounds exhibited some capacity to inhibit the proliferation of live parasites in erythrocytes, albeit at levels an order of magnitude higher than those exhibited on the enzyme. The major problem, however, was that counterscreening them on a panel of 80 Human kinases showed that they are promiscuous inhibitors of many potentially undesirable off-target kinases. 

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