BAY-1797
| Target | P2RX4 |
| Mode of action | Inhibitor |
| Control | BAY-207 |
| Recommended cellular usage concentration | 0.1 - 1 µM |
| In vivo use | yes |
| Donated by | Bayer |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Potency as inhibitor of P2X4 ion channel demonstrated in FLIPR assay: Human P2RX4 IC50 at 211 nM (HEK, Ca2+) and at 108 nM (1321N1 astrocytoma, Ca2+)Equipotent on human, rat (IC50 = 233 nM) and mouse (IC50 = 112 nM) P2RX4 |
| Selectivity within target family: > 30-fold | Surpasses criterion: Selectivity against family members was tested, all > 30 fold (P2RX1 (IC50 > 50 µM), P2RX2 (IC50 > 30 µM), P2RX3 (IC50 = 8.3 µM), P2RX7 (IC50 = 10.6 µM)) |
| Selectivity outside target family | Surpasses criterion: Selectivity in Eurofins Lead Profiling Screen, GPCR Profiling Screen and Bayer Kinase Panel was performed (only relevant IC50: SLC6A3 2.2 µM)Closest hits in the PDSP scan are ADRA2B (Ki = 4285.88 nM) and TMEM97 (Ki = 4344.21 nM). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Ephys human P2RX4 IC50 = 274 nM (Qpatch, HEK cells); Patch-clamp experiments on human P2X4 IC50 = 320 nM (QPatch, 1321N1 cells) Efficacy in several in vitro and in vivo mechanistic models was demonstrated. |
| Control compound (100 times less potent than the probe) | Surpasses criterion: Structure related compound BAY-207 with no P2RX4 activity (human P2RX4 IC50 > 25 µM (HEK, Ca2+). Shows off-target activity in the PDSP scan: the closest hits are GABA/PBR (Ki= 250.13 nM) and ADRA2C (Ki= 654.33 nM) |