BI-8668
Probe criteria
| Selectivity outside target family | Cerep SafteyScreen (50 targets) at 10 µM [% ctrl]: CHRM3 (20), CHRM2 (36), ADRA1A (45), others > 50Clean PDSP scan (43 targets at 10 µM) except for HRH3 (Ki = 256.83 nM). |
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: IC50 = 17 nM (Inhibition of Na+ current by Ussing Chamber - MucilAir™ P0: IC50 were derived form a 5-steps concentration curve (1 nM -> 10,000 nM; n=6)) |
| Selectivity within target family: > 30-fold | No closely related protein identified. |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Inhibition of M-1 water resorption: 81 % inhibition (Measurement of ENaC-mediated water permeability through cell monolayers of M-1 cells and the blocking capacity of ENaC-inhibitors. The transported volume is determined with tritiated water. A potent ENaC-inhibitor results in reduced water transport leading to more remaining liquid in the apical (upper) compartment of the cell layer.) |
| Control compound (100 times less potent than the probe) | BI-0337: IC50 > 10 µM (Ussing chamber)Eurofins SafteyScreen (44 targets) at 10 µM [% ctrl]: SLC6A4 (31), CHRM3 (35), ACE (39), CHRM2 (41), others > 50 |