Half-maximum inhibitory concentrations (IC50) for the exploratory compound on wild-type hNav1.4 channels, F1586C, and Y1593C hNav1.4 mutants
The IC50 values and slope factors (nH) were calculated from the fit of concentration-effect relationships with eq. 1 at stimulation frequencies of 0.1 and 10 Hz. The 0.1-to-10-Hz IC50 ratio is reported.
| Channel type | Drug | 0.1 Hz | 10 Hz | |||
|---|---|---|---|---|---|---|
| IC50 | nH | IC50 | nH | IC50 ratio | ||
| µM | µM | |||||
| Wild-type | Lubeluzole | 39.7 ± 0.2 | 0.9 ± 0.2 | 1.5 ± 0.1 | 0.9 ± 0.1 | 26.5 |
| R isomer | 35.7 ± 3.7 | 1.2 ± 0.1 | 2.8 ± 0.2 | 1.1 ± 0.1 | 12.8 | |
| R,S-lubeluzole | 30.6 ± 5.1 | 0.9 ± 0.1 | 1.7 ± 0.2 | 1.3 ± 0.2 | 18.0 | |
| A-core | 457 ± 121 | 0.9 ± 0.2 | 221 ± 53 | 1.1 ± 0.3 | 2.1 | |
| R-like | 712 ± 51 | 2.0 ± 0.3 | 615 ± 86 | 2.0 ± 0.4 | 1.2 | |
| Riluzole | 50.0 ± 7.8 | 1.7 ± 0.4 | 42.8 ± 3.2 | 1.7 ± 0.2 | 1.2 | |
| F1586C | R,S-lubeluzole | 107 ± 11 | 1.3 ± 0.1 | 10.4 ± 1.3 | 0.8 ± 0.1 | 10.3 |
| A-core | 523 ± 45 | 0.9 ± 0.1 | 472 ± 41 | 0.9 ± 0.1 | 1.1 | |
| Riluzole | 127 ± 10 | 2.5 ± 0.5 | 111 ± 7 | 3.1 ± 1.0 | 1.2 | |
| Y1593C | R,S-lubeluzole | 36.1 ± 1.0 | 1.7 ± 0.1 | 4.6 ± 0.8 | 1.1 ± 0.1 | 7.8 |