Table 1. Potency and selectivity of synthetic ProTX-II and JNJ63955918.
| Peptide | hNav1.7 | hNav1.1 | hNav1.2 | hNav1.3 | hNav1.4 | hNav1.5 | hNav1.6 | |
|---|---|---|---|---|---|---|---|---|
| ProTX-II QP | pIC50 | 9.1 ± 0.06 | 7.8 ± 0.08 | 7.1 ± 0.07 | 7.6 ± 0.09 | 7.1 ± 0.07 | 6.4 ± 0.07 | 7.5 ± 0.04 |
| Fitted Emax (%) | 88.8 ± 3.1 | 100 | 100 | 100 | 100 | 100 | 100 | |
| Fold Nav1.7 Selectivity | — | 19.8 | 99.3 | 31.4 | 99.3 | 497.6 | 39.5 | |
| JNJ63955918 QP | pIC50 | 8.0 ± 0.09 | 5.2 ± 0.13 | 6.1 ± 0.38 | nd | 4.8 ± 0.13 | <5.5 | 5.6 ± 0.11 |
| Fitted Emax (%) | 79.1 ± 3.4 | 100 | 27.6 ± 7.3 | nd | 100 | 100 | ||
| Fold Nav1.7 Selectivity | — | 631 | 79.4 | nd | 1584.9 | >316.2 | 251.2 | |
| JNJ63955918 MPC | pIC50 | 8.0 ± 0.08 | 5.0 ± 0.06 | 5.8 ± 0.46 | nd | 5.3 ± 0.11 | <5.0 | 6.0 ± 0.04 |
| Fitted Emax (%) | 94.8 ± 3.3 | 100 | 50.0 ± 18.5 | nd | 100 | 100 | ||
| Fold Nav1.7 Selectivity | — | 1000 | 158.5 | nd | 501.2 | >1000 | 100 |
(IC50 is defined as the concentration to produce inhibition equivalent to 50% of the fitted Emax).
QP = IC50 determined by automated electrophysiology using QPatch.
MPC = IC50 determined by conventional manual patch-clamp electrophysiology.
Fold Nav1.7 selectivity = 10^(Nav1.7 pIC50 − Nav1.x pIC50).