TABLE 2
Trp-based derivatives that induced Ca2+ mobilization in human neutrophils and FPR-transfected HL-60 cells
The EC50 values are presented as the mean ± S.D. of three independent experiments, in which median effective concentration values (EC50) were determined by nonlinear regression analysis of the dose-response curves (five to six points) generated using GraphPad Prism 5 with 95% confidence interval (P < 0.05). Efficacy is expressed as percentage of the response induced by 5 nM fMLF (FPR1) or 5 nM WKYMVm (FPR2 and FPR3).
| Compound | R1 | R2 | Enantiomer | Ca2+ Mobilization, EC50, and Efficacy | |||
|---|---|---|---|---|---|---|---|
| Neutrophils | FPR1 | FPR2 | FPR3 | ||||
| μM (%) | |||||||
| AG-10/1 | H |  | R/S | 3.8 ± 0.5 (120) | 2.7 ± 0.4 (100) | 0.3 ± 0.07 (115) | 13.5 ± 3.4 (60) |
| AG-10/2 | Br |  | S | 1.9 ± 0.5 (125) | 0.5 ± 0.1 (120) | 0.13 ± 0.03 (120) | 7.6 ± 1.9 (85) |
| AG-10/3 | Br |  | S | 2.7 ± 0.6 (135) | 2.2 ± 0.6 (120) | 0.3 ± 0.06 (110) | 2.4 ± 0.5 (80) |
N.A., nonactive compound (cell activation was <30% of control level over a concentration range of 0–40 μM).
*Location of the chiral center.