BE‐23372M, a Novel and Specific Inhibitor for Epidermal Growth Factor Receptor Kinase

The fungal metabolite BE‐23372M is a structurally novel protein kinase inhibitor. Its IC(50) for epidermal growth factor (EGF) receptor kinase was 0.03 μM. IC(50) values of BE‐23372M for other protein tyrosine kinases, erbB‐2, p43(v‐abl), insulin receptor kinase, and p60(c‐src) were 0.42, 1.0, 3.3, and 4.5 μM, respectively, and the IC(50) for protein kinase C, a serine/threonine kinase, was 4.1 μM. Cdc2 kinase, casein kinases I and II and cAMP‐dependent protein kinase were not inhibited by 20 μM BE23372M. A kinetic study showed that BE‐23372M was competitive with respect to the substrate peptide and to ATP. Autophosphorylation of solubilized EGF receptor kinase was clearly inhibited by 0.1 μM BE‐23372M. Autophosphorylation of EGP receptor in A431 cells was also inhibited. These results show that BE‐23372M is a potent and specific EGF receptor kinase inhibitor. It should be a valuable tool for EGF receptor kinase research.