National Center for
3K3J: P38alpha Bound to Novel Dfg-out Compound Pf-00416121
The design, synthesis and potential utility of fluorescence probes that target DFG-out conformation of p38alpha for high throughput screening binding assay
Chem Biol Drug Des (2009) 74 p.547-559
The design, synthesis and utility of fluorescence probes that bind to the DFG-out conformation of p38alpha kinase are described. Probes that demonstrate good affinity for p38alpha, have been identified and one of the probes, PF-04438255, has been successfully used in an high throughput screening (HTS) assay to identify two novel non-classical p38alpha inhibitors. In addition, a cascade activity assay was utilized to validate the selective binding of these non-classical kinase inhibitors to the unactive form of the enzyme.