PF-05105679
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Inhibition of binding to TRPM8: IC50 = 103 nM |
| Selectivity within target family: > 30-fold | Selective over related family at 10 µM: TRPV1, TRPA1 (Ca+ mobilization assays and single-cell patch-clamp studies against both voltage-and agonist-driven activation) Clean Millipore Ion channel CardiacProfiler panel at 10 µM. |
| Selectivity outside target family | Clean CEREP Ligand Profile screen (90 targets): No greater than 36 % inhibition at 10 µM for any off-target.One hit in the PDSP scan: GABA/PBR (Ki = 1022.12 nM) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Inhibition of voltage-induced current in HEK-293 cells expressing human and guinea pig TRPM8 channels. Avg IC50s derived from these curves were 103 (± 29.4) nM for humans and 109 ± 38.8 nM for guinea pigs. PF-05105679 exhibited a mean IC50 of 13.8 ± 2.2 nM on voltage activation in HEK-293 cells at 12°C. |
| Control compound (100 times less potent than the probe) | PF-05257137 with IC50 > 10 µM;Clean PDSP scan |