BI-2081
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | FFAR1: Ki = 23 nM (biochemical assay) |
| Selectivity within target family: > 30-fold | Eurofins Safety Panel (44 GPCRs at 10 μM): Closest off-targets (Kd [µM]): ADRA2C (0.840), ADRA2A (1.3), CHRM3 (2.9); HRH1 (3.1), PTGER4 (4.6), ADRA2B (21)Clean PDSP scan (43 targets at 10 µM). |
| Selectivity outside target family | Eurofins Safety Panel (29 receptor/channel targets at 10 μM): Closest off-targets (Kd [µM]): PPARG (0.470), THRA (rat, 3.5) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | EC50 = 3-5 nM (human IPOne assay: Stimulation of 1321N1 cells, which express FFAR1 followed by measurement of the IP1 accumulation by fluorescence) |
| Control compound (100 times less potent than the probe) | BI-0340: EC50 = 1230 nM (human IPOne assay); Eurofins Safety Panel 44™: clean (closest off-target: NR3C1 (57 % inh. at 10 µM))Clean PDSP scan (43 targets at 10 µM). |