Table 4.
Compound | R1 | R2 | R3 | R4 | PfPK6 IC50 (nM)a | Pf3D7 blood stage EC50 (nM)b |
---|---|---|---|---|---|---|
Ki8751 | H | F | H | F | 14 ± 1 | n.d. |
39 | CF3 | H | H | H | 0.84 ± 0.04c | 540 ± 24 |
40 | CF3 | H | H | F | 1.2 ± 0.07c | Inactived |
41 | H | H | H | 13 ± 0.5 | 580 ± 65 | |
42 | H | H | H | 23 ± 1 | Inactivee | |
43 | H | H | H | 321 ± 21 | Inactivee | |
44 | H | H | H | 68 ± 3 | Inactivee | |
45 | CF3 | H | H | 1.9 ± 0.1c | 110 ± 4 | |
46 | CF3 | H | H | 0.81 ± 0.02c | 410 ± 23 | |
47 | CF3 | H | H | 21 ± 1 | Inactivee | |
48 | CF3 | H | H | 0.29 ± 0.02c | Inactivee |
IC50 values were determined using the KinaseSeeker assay with 5-fold dilutions, presented as mean ± s.e.m. values of two experiments performed in duplicate.
EC50 values were determined using the SYBR Green I-based assay with 2-fold dilutions, presented as mean ± s.e.m. values performed in triplicate.
IC50 values approach the kinase concentration in the assay. IC50s < 5 nM treated as equipotent.
No inhibition when tested up to 5 μM in two experiments, testing in dose-response manner.
No inhibition when tested in triplicate at a single concentration of 1 μM. n.d. = not determined.