BAY-390
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: FLIPR Ca2+ assay (CHO or HEK cells): human TRPA1 IC50 = 16 nM, dog IC50 = 19 nM, rat IC50 = 63 nM; Equipotent on rat, mouse, guinea pig and monkey TRPA1. |
| Selectivity within target family: > 30-fold | Surpasses criterion: Selectivity against family members was tested, all > 30 fold: hTRPV1 IC50 > 25 µM, hTRPV4 IC50 > 25 µM, hTRPC3 IC50 > 25 µM, hTRPC5 IC50 = 5.6 µM, hTRPC6 IC50 > 25 µM, hKCNK9 (TASK-3) IC50 > 30 µM, hCACNA1H (Cav3.2) IC50 > 25 µM |
| Selectivity outside target family | Selectivity in Eurofins Lead Profiling Screen, GPCR Profiling Screen and Bayer Kinase Panel was performed. Closest off-targets: SLC6A3 (human) Ki = 0.9 μM, PGR (human) Ki = 4 μM, ESR1 EC50 = 2.1 μMTwo off-targets in the PDSP scan: SLC6A3 Ki = 1377.15 nM, HTR2A Ki = 2576.32 nM |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Ephys human TRPA1: IC50 = 82 nM (Patchliner, CHO cells) |
| Control compound (100 times less potent than the probe) | Surpasses criterion: BAY-9897: FLIPR Ca2+ assay (CHO or HEK cells): human TRPA1 IC50 > 25 µMClean PDSP scan with one weak exception: HRH2 Ki = 9781.38 nM |