BAY-439
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Biochemical assay using recombinant PLA2G5 and Red/Green BODIPY® PC-A2 as substrate: PLA2G5 human (IC50 = 7 nM), mouse (IC50 = 8 nM), rat (IC50 = 18 nM); Binding (SPR): human PLA2G5 (KD = 214 nM) |
| Selectivity within target family: > 30-fold | Biochemical assay: human PLA2G4A (IC50 >40 µM), PLA2G7 (IC50 > 40 µM), PLA2G2A (IC50 = 0.788 µM), PLA2G10 (IC50 = 2.85 µM);Nuvisan Phospholipase C panel: human PLCB3/PLCD1/PLCG1 / PLCZ1 (all IC50 >20 µM) |
| Selectivity outside target family | Eurofins Bayer Safety Screen (77 targets) at 10 µM: Closest off-targets: human SLC6A3 (82 % inhibition, IC50 = 3.55 μM), ADRA2C (74 % inhibition, IC50 = 3.07 μM), human PGR (79 % inhibition, IC50 = 1.19 μM), human SLC6A2 (76 % inhibition, IC50 = 4.71 μM); Kinase panel (378 kinases) at 10 μM: Closest off-targets are DYRK1A (58 % inhibition) and CSNK2A1 (55 % inhibition) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Cellular PLA2G5 assay using THP-1 cells and Bis-BODIPY® FL C11-PC: IC50 = 61 nM |
| Control compound (100 times less potent than the probe) | BAY-163: Biochemical assay: PLA2G5 human (IC50 > 25 µM), mouse/rat (IC50 > 20 µM), human PLA2G4A (IC50 >40 µM), PLA2G7 (IC50 > 40 µM), PLA2G2A (IC50 = 24.1 µM), PLA2G10 (IC50 = 14.3 µM);Nuvisan Phospholipase C panel: human PLCB3/PLCD1/PLCG1 / PLCZ1 (all IC50 >20 µM); Binding (SPR): human PLA2G5 (KD > 10 µM); Eurofins Bayer Safety Screen (77 targets) at 10 µM: Closest off-targets: human SLC6A3 (52 % inhibition), ADRA2C (54 % inhibition), Adenosine transporter (88 % inhibition) Kinase panel (378 kinases) at 10 μM: Closest off-target is DYRK1A (52 % inhibition) |