BI-4394
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | MMP13: IC50 = 1 nM (FRET assay) |
| Selectivity within target family: > 30-fold | Highly selective (> 1000-fold) against other matrix metalloproteinases: MMP1 (IC50 > 22 µM), MMP2 (18 µM), MMP3 (> 22 µM), MMP7 (> 22 µM), MMP8 (> 22 µM), MMP9 (8.9 µM), MMP10 (16 µM), MMP12 (> 22 µM) and MMP14 (8.3 µM) |
| Selectivity outside target family | Invitrogen Panel: 18/56 kinases hit > 50 % inhibition at 10 µM, most potent off targets: AURKA (1.3 µM), MAPKAPK2 (1.1 µM), PRKAA1 (1.9 µM), PRKACA (1.6 µM); Clean PDSP scan |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Bovine nasal cartilage (BNC) degradation assay (ELISA, inhibition of full-length MMP-13-induced cartilage degradation): IC50 = 31 nMMMP13 collagen degradation assay (Rapid Collagen Assay from Condrex, full length MMP13): IC50 = 11 nM |
| Control compound (100 times less potent than the probe) | BI-4395: IC50 > 26 µM; Clean PDSP scan |