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 microM. 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 microM, respectively, and the IC50 for protein kinase C, a serine/threonine kinase, was 4.1 microM. Cdc2 kinase, casein kinases I and II and cAMP-dependent protein kinase were not inhibited by 20 microM 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 microM 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.
Tanaka
S
S
Banyu Tsukuba Research Institute, Merck Research Laboratories, Tsukuba.
Okabe
T
T
Chieda
S
S
Endo
K
K
Kanoh
T
T
Okura
A
A
Yoshida
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009036:Moths; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D014407:Tumor Cells, Cultured
D005663:Furans; D010636:Phenols; D047428:Protein Kinase Inhibitors; C087122:BE 23372M; D004815:Epidermal Growth Factor; D066246:ErbB Receptors