Table 1. EC50s of compound 1 and its analogues.
| compound # | CID | structure derivation | Rab7 | H-Ras | H-Ras G12V | Cdc42 | Cdc42 Q61L | RhoA | Rac1 | Rac1 Q61L |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 1067700 | X = O;R1 = Me;R2 = Me;R3 = OH;R4 = CS-NH-CO; R5 = phenyl | 0.12 ± 0.055 | 0.16 ± 0.16 | 0.052 ± 0.044 | 1.09 ± 1.62 | 0.047 ± 0.038 | 0.062 ± 0.049 | 0.062± 0.049 | 0.075 ± 0.059 |
| 1a | 1067700 | X = O;R1 = Me;R2 = Me;R3 = OH;R4 = CS-NH-CO; R5 = phenyl | 0.43 | 0.24 | 0.26 | 0.42 | 0.35 | 0.10 | 0.099 | 0.12 |
| 2 | 1251121 | R3 = OMe | >1000 | >1000 | >1000 | >1000 | >1000 | NA | NA | NA |
| 3 | 46916266 | R1 = H;R2 = H | 0.16 ± 0.067 | 0.17 ± 0.094 | 0.12 ± 0.12 | 0.11 ± 0.064 | 0.13 ± 0.078 | 0.23 ± 0.21 | 0.18 ± 0.13 | 0.23 ± 0.22 |
| 4 | 740871 | R4 = CO-CH2 | >1000 | >1000 | >1000 | >1000 | >1000 | NA | NA | NA |
| 5 | 1280844 | R4 = CS-NH | NA | NA | 3.55 | 391.00 | 125.70 | 1.39 | 4.06 | 1.66 |
| 6 | 46916265 | R4 = CO-NH-CO | 0.31 ± 0.09 | 0.44 ± 0.41 | 0.49 ± 0.48 | 17.00 | 0.47 | 0.33 ± 0.03 | 0.35 ± 0.05 | 0.40 ± 0.02 |
| 7 | 53301934 | R5 = 3-MeO-phenyl | 0.15 ± 0.13 | 0.13 ± 0.13 | 0.12 ± 0.12 | 0.58 ± 0.83 | 0.50 ± 0.71 | 0.20 ± 0.13 | 0.19 ± 0.06 | 0.22 ± 0.14 |
| 8 | 53301932 | R5 = 4-MeO-phenyl | 0.14 ± 0.07 | 0.14 ± 0.09 | 0.17 ± 0.10 | 1.2 ± 1.0 | 0.23 ± 0.039 | 0.15 ± 0.06 | 0.13 ± 0.06 | 0.15 ± 0.09 |
| 9 | 53377405 | R5 = 4-F-phenyl | 0.41 ± 0.19 | 0.33 ± 0.22 | 0.091 | 1.0± 1.2 | 0.88 ± 0.47 | 0.11 | 0.15 | 0.13 |
| 10 | 53301931 | R5 = 2-Br-phenyl | 0.43 ± 0.68 | 0.62 ± 1.00 | 0.43 ± 0.68 | 46.77 ± 66.01 | 14.76 ± 20.80 | 0.48 ± 0.74 | 0.60 ± 0.80 | 0.42 ± 0.65 |
| 11 | 53377404 | R5 = 2-Me-phenyl | 0.41 | 0.44 | 0.38 | 2.66 | 1.35 | 0.49 | 0.44 | 0.37 |
| 12 | 53301933 | R5 = 4-Br-phenyl | 0.30 ± 0.18 | 0.33 ± 0.24 | 0.32 ± 0.22 | 25.86 ± 44.07 | 10.89 ± 18.37 | 0.32 ± 0.13 | 0.26 ± 0.11 | 0.28 ± 0.15 |
Derivatization sites were indicated in Fig 1. Compound numbers are used in the main text for convenience. For EC50s with standard deviations, the values were the averages from multiple measurements. In multiple repetitions, variability was observed with Cdc42, which increased its EC50 average. Therefore, the biochemical data for Cdc42 when needed for comparison is from a single set of experiment (Table 2 and Fig 2). For EC50s without standard deviations, the values were determined from one measurement carried out in duplicate where all the data points were used to fit the sigmoidal dose-response equation. EC50 values were noted NA when they were not available or data could not give acceptable fit.
aThe concentration dependence on BODIPY-FL GDP.