Compounds 2-4 were designed to improve the selectivity of TCMDC-135051 (1) by targeting a poorly conserved cysteine, Cys368. Chloroacetamide 4 was therefore screened against a representative panel of 58 human kinases from across the kinome, using Eurofins Discovery's KinaseProfiler technology. Fig. compares the selectivity scores (S(50), S (30) and S( )) of 4 and TCMDC-135051 (1). S(x) represents the fraction of kinases with less than x% remaining activity when treated with 1 μM compound. These data show compound 4 to have a significant improvement in selectivity relative to TCMDC-135051 (1), with no kinases being inhibited below 20% remaining activity at 1 μM, and only 1 kinase below 30% activity (Fig. , Table ). Kinases inhibited below 50% activity by compound 4 are shown on the human kinome phylogenetic tree (Fig. ). This implies that targeting of Cys368 can improve selectivity for PfCLK3 over the human kinome. Furthermore, using the KINOMEscan TM technology (Fig. proved substantially less cytotoxic than TCMDC-13501 (1) (pEC50 5.80 ± 0.14),