BE-23372M, A NOVEL PROTEIN-TYROSINE KINASE INHIBITOR .1. PRODUCING ORGANISM, FERMENTATION, ISOLATION AND BIOLOGICAL-ACTIVITIES

BE-23372M, a novel protein tyrosine kinase inhibitor, was isolated fro m the culture broth of a fungus. The producing strain, F23372, was ide ntified as Rhizoctonia solani, based on the cultural and morphological characteristics. The active principle was extracted from the mycelium with acetone and purified by solvent extraction, silica gel column ch romatography and Sephadex LH-20 column chromatography. BE-23372M showe d strong inhibitory activity against EGF receptor kinase with IC50 val ues of 0.02 and 0.03 muM on two different substrates, whereas IC50 val ues against protein kinase C and cAMP-dependent protein kinase were 4. 5 and >20 muM, respectively. The compound inhibited the growth of A431 human epidermoid carcinoma and MKN-7 human stomach cancer cell lines with IC50 values of 8 and 24 muM, respectively.