Comparison of predicted and experimentally derived IC50 values of MLA analogs
Predicted IC50 values were calculated using the CoMFA model. Inhibition curves were generated as described under Materials and Methods; values represent geometric means (confidence limits), n = 4 to 6. Competition binding experiments were performed with a fixed concentration of each analog (10 μM), as described under Materials and Methods; values represent arithmetic means ± S.E.M., n = 4.
Analog | IC50 Values | Native nAChR Specific Binding | ||||
|---|---|---|---|---|---|---|
| CoMFA Prediction | Native nAChR Nicotine-Stimulated Neurosecretion | Recombinant nAChR Nicotine-Stimulated [Ca2+]i | ||||
| μM | % Control | |||||
| COB 1 | 2.7 | 3.5 (3.1-3.9) | 1.2 (1.0-1.4) | 113.5 ± 4.8 | ||
| COB 2 | 9.8 | 1.2 (1.2-1.3) | 1.1 (1.0-1.1) | 125.8 ± 3.8 | ||
| COB 3 | 6.1 | 3.0 (2.5-3.7) | 0.7 (0.6-0.9) | 106.0 ± 2.5 | ||
| DDR 1 | 11.5 | 1.7 (1.4-2.0) | 30.0 (23.5-38.3) | 118.7 ± 13.9 | ||