BAY-7081
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Human PDE9A: IC50 = 15 nM (3H-cAMP and 3H-cGMP Scintillation Proximity Assay (SPA)); Mouse IC50 = 34 nM; Rat IC50 = 42 nM |
| Selectivity within target family: > 30-fold | Bayer in-house PDE panel [IC50 [µM]]: bovine PDE1(0.753), PDE2A (> 10), PDE3B (> 10), PDE4B (3.96), PDE5A (2.98), bovine PDE6 (1.56), PDE7B (> 10), PDE8A (1.49), PDE10A (> 10), PDE11A (6.6) |
| Selectivity outside target family | Eurofins Panlabs panel (75 targets) at 10 µM: clean In-house kinase panel (31 kinases): 1 x IC50 = 6.6 µM, others IC50 > 20 µMSGC Tm panel (DSF) at 10 µM (99 targets): cleanClean PDSP scan (43 targets at 10 µM). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Cellular PDE9A assay: EC50 = 995 nM (mouse) |
| Control compound (100 times less potent than the probe) | BAY-7424: Distomer: IC50 > 10 µM (biochemical assay); EC50 > 10 µM (cellular assay); PDE1-11 at Panlabs at 10 µM: clean except for PDE9A (62% inhibition); In-house kinase panel (31 kinases): cleanSGC Tm panel (DSF) at 10 µM (99 targets): clean. The PDSP scan (43 targets at 10 µM) is clean except for OPRM1 (Ki = 4713.28 nM). |