BAY-784
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Surpasses criterion: human GnRHR: IC50 = 27 nM (Tag Lite binding assay) |
| Selectivity within target family: goal is > 30-fold | Surpasses criterion: Selectivity against a broad range of GPCR‘s. Clean PDSP scan except for weak activity on TMEM97 (Ki = 1107.9 nM) Eurofins-Panlabs radioligand binding assay: The closest off-target is CNR1 with IC |
| Selectivity outside target family | Surpasses criterion: Eurofins-panlabs enzyme assay: The closest off-targets found at 10 µM are MAPK3 with IC50= 4.87 µM and MAPK14 with IC50 = 10.7 µM. |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: High potency in human cell-based IP-1 assay with IC50 of 21 nM (superagonist Buserelin stimulation at EC80). Suitable pharmacokinetic profile for in vivo studies; in vivo efficacy in LH suppression experiments in female rats and male monkeys shown. |
| Control compound (100 times less potent than the probe) | Surpasses criterion: The control compound BAY-786 has at least 114-fold lower in vitro potency (IC50 = 2.4 μM). Clean PDSP scan except for weak activity on TMEM97 (Ki = 2001.24 nM) |