TABLE 2 .
Selection compounda/test compound and mutant | IC50, µM (SEM)b |
P value (method 3) | MIC50 (µM)c |
P value (method 4d) | ||
---|---|---|---|---|---|---|
Wild type | Mutant | Wild type | Mutant | |||
F3215-0002/I-BET151 | ||||||
3-R1A2 | 7.6 (1.04) | 328.7 (28.1) | 3.1E−06 | 12.5 | None | 1.9E−05 |
1-RB10 | 14.9 (1.07) | 71.6 (1.94) | 5.8E−09 | 25 | None | 4.7E−10 |
2-R3C3 | 12.5 (1.03) | 82.1 (1.17) | 7.0E−11 | 12.5 | None | 0.0060 |
I-BET151/F3215-0002 | ||||||
1-4F10 | NDf | 3.17 (1.08) | ND | 1.1 | 3.3 | 0.12 |
2-5H11 | 0.61 (1.07) | 1.03 (1.97) | 0.85 | 1.1 | 3.3 | 0.062 |
3-1C6 | 1.08 (1.15) | 2.20 (1.33) | 0.54 | 1.1 | 3.3 | 0.448 |
4-4G12 | 0.48 (1.19) | 5.81 (1.10) | 0.011 | 1.1 | 10 | 1.8E−07 |
5-2A8 | 0.87 (1.03) | 2.59 (1.26) | 0.32 | 1.1 | 3.3 | 1.1E−04 |
6-3E6 | 0.58 (1.10) | ND | ND | 1.1 | 3.3 | 1.2E−05 |
A 10 µM concentration of F0002 and a 100 µM concentration of I-BET151 were used for selection.
IC50 calculated for use in method 3 (see reference 48 and Materials and Methods) directly comparing IC50 values when available for both mutant and wild-type parasites.
Minimum concentration that resulted in >50% growth inhibition compared to the untreated controls.
P value comparing entire dose-response curves for each mutant to the wild-type parent using method 4 (see reference 48 and Materials and Methods). For each mutant, a separate wild-type assay was conducted in parallel.
IBETR mutants were challenged with F0002, and F0002-resistant mutants were challenged with I-BET151.
ND, not determined.