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 IC50 for epidermal growth factor (EGF) receptor kinase was 0.03 nuM. IC50 values of BE-23372M for other protein tyrosine kinases, erbB-2, p43v-abl, insulin receptor kinase, and p60c-src were 0.42, 1.0, 3.3, and 4.5 muM, respectively, and the IC50 for protein kinase C, a serine/threonine kinase, was 4.1 muM. Cdc2 kinase, casein kinases I and II and cAMP-dependent protein kinase were not inhibited by 20 muM BE-23372M. 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 muM BE-23372M. Autophosphorylation of EGF 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.