BI-5524
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | IC50 = 0.5 nM (human ELANE inhibitor assay); Mouse: IC50 = 12 nM |
| Selectivity within target family: > 30-fold | Highly selective against closely related proteases: PRTN3 (proteinase 3; IC50 = 367 nM) and CTSG (cathepsin G; IC50 >10 μM)Reaction Biology protease panel with 43 targets at 1 µM: clean (ELANE:-0.46 % enzyme activity) |
| Selectivity outside target family | Eurofins Cerep screen with 81 targets at 10 μM: clean |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Inhibition of zymosan-stimulated ELANE activity in human plasma: IC50 =1.2 nM |
| Control compound (100 times less potent than the probe) | BI-5525: IC50 = 41 nM (human ELANE inhibitor assay) 82-fold; Inhibition of zymosan-stimulated ELANE activity in human plasma: IC50 = 492 nMEurofins screen with 44 targets: ≤ 50% inhibition at 10 μMReaction Biology protease panel with 43 targets at 1 µM: clean (ELANE: 8.3 % enzyme activity) |