BAY 1753011
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Binding assay: AVPR1A (Ki = 0.5 nM), AVPR2 (Ki = 0.6 nM) |
| Selectivity within target family: > 30-fold | Binding assay: ADRA1B (Ki > 10 µM), OXTR (Oxytocin receptor, Ki = 5.1 nM). An oxytocin antagonist (Ki 4.6 nM, selectivity vs AVPR1A and AVPR2 > 695) is available L-371,257<7br>Closest off-targets in the PDSP screen (43 targets at 10 µM) are SLC6A2 (Ki = 1316.15 nM), OPRK1 (Ki = 2166.66 nM) and GABAA/BZP (Ki = 2609.76 nM) |
| Selectivity outside target family | Eurofins Panlabs safety screen of >120 targets at 10 µM: clean Eurofins kinase panel (378 kinases) at 10 µM: Closest off-target NEK3 (61% inh.) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Cell-based assay with bioluminescence detection: hAVPR1A IC50 = 3.6 nM; hAVPR2 IC50 = 1.7 nM |
| Control compound (100 times less potent than the probe) | BAY-2297: Binding assay: AVPR1A (Ki > 10 µM), AVPR2 (Ki > 10 µM); Cell-based assay: AVPR1A (IC50 > 10 µM); AVPR2 (IC50 > 10 µM); AVPR1B (Ki > 10 µM), OXTR (Ki > 10 µM)Eurofins Panlabs safety screen of 80 targets at 10 µM: clean; Eurofins kinase panel (378 kinases) at 10 µM: cleanClean PDSP screen (43 targets at 10 µM) |