BE-23372M

The fungal metabolite BE‐23372M is a structurally novel protein kinase inhibitor. Its IC50 for epidermal growth factor (EGF) receptor kinase was 0.03 μM. 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 μM, respectively, and the IC50 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.

BE-23372M, a new protein tyrosine kinase inhibitor, has been obtained as a reddish orange solid. The compound, C17H12O6, HRFAB-MS: m/z 312.0625 (M)+, is an acidic substance, showing UV (MeOH) lambda max (epsilon) 266 (8,800), 426 nm (20,400), and IR (KBr)vmax 1752(C = O) and 3298(OH) cm-1. The structure of BE-23372M, (E)-3-(3,4-dihydroxybenzylidene)-5-(3,4-dihydroxyphenyl)-2(3H)-fur anone, has been elucidated by 1H and 13C NMR studies.