PF-04554878
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Binding IC50 = 0.2 nM (PTK2 and PTK2B) versus recombinant human enzyme kinase domain |
| Selectivity within target family: > 30-fold | Profiling against an Invitrogen panel at 10 µM and 1 µM: Strongest inhibition found for NTRK1 (IC50 = 56 nM) and MAP3K9 (IC50 = 75.3 nM) |
| Selectivity outside target family | Cerep profile against 122 human receptors, ion channels, enzymes, and uptake sites: the closest off-target is ADORA3 (Adenosine A3) (Ki = 27 nM); Clean PDSP scan |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | NanoBRET assay (SGC Frankfurt):PTK2 (EC50 = 28 ± 4.4 nM), PTK2B (EC50 = 520 ± 85 nM)Inhibits PTK2 phosphorylation in A431 cells (IC50 = 3 nM); Inhibition also conducted in various xenografts where % tumor growth inhibition was measured. |
| Control compound (100 times less potent than the probe) | PF-00911705 - Binding IC50 = 721 nMNanoBRET assay (SGC Frankfurt):PTK2 (EC50 = 3.2 ± 0.3 µM), PTK2B (EC50 = 37 ± 7.1 µM)Two hits in the PDSP scan: GABA/PBR (Ki = 1479.11 nM) and TMEM97 (Ki = 2123.24 nM). |