Table 1. Summary of biochemical, cellular, and biophysical measures of potency in μM.
| Compound 1 | Compound 2 | Compound 3 | Compound 4 | Compound 5 | Compound 6 | |
|---|---|---|---|---|---|---|
| Coupled assay IC501 | 87±22 (N = 8) | 0.8±0.7 (N = 18) | 1.2 (1.8;0.8) | 49 (>25;49) | 7 (7.0;7.0) | 133 (>50;133) |
| Counter-screen IC501 | >250 (N = 11) | 85±47 (N = 3) | >25 (>25;>25) | 115 (>25;115) | 29 (30;29) | 134 (>50;134) |
| Growth inhibition EC502 | >30 | 2.7±1.4 (N = 3) | 1.2 | >30 | 18 | >30 |
| Kd BLI3 | ND | 0.8 | 2.6±0.8 (N = 10) | >10 | 34 | 1,100 |
| Kd HSQC | ND | 690 (603;776)4 | ND | ND | 1,1005 | 3406 |
Data for the coupled assay and for the growth inhibition assay, as well as the Kd from BLI reflect experiments with full-length prenylated GTPγS -loaded KRAS in a lipid environment. The Kd from HSQC reflects experiments with non-processed GDP-loaded KRAS in aqueous buffer. The counter-screen is the BRAFV600E counter-screen. ND = Not Determined.
1IC50 values are shown as the geomean where at least two non-qualified values were available, with individual IC50 values shown in parentheses for every compound done with N = 2 and geomean ± standard deviation shown for compounds 1 and 2.
2EC50 values are shown from curve-fitting where each concentration was run in triplicate and all points were used for fitting a single curve; EC50 value for compound 2 is shown as the geomean ± standard deviation from three independent assays.
3BLI measurements were performed in singleton after establishing reproducibility for compound 3, which is shown as geomean ± standard deviation.
4Average value calculated from the shifts obtained from fitting the data related to two separate peaks (individual values noted in parentheses).
5Reference [19].
6Reference [18].