Open AccessBE‐23372M, a Novel and Specific Inhibitor for Epidermal Growth Factor Receptor Kinase
Author(s) -
Tanaka Seiichi,
Okabe Takayoshi,
Chieda Shinya,
Endo Kaori,
Kanoh Tomoko,
Okura Akira,
Yoshida Eisaku
Publication year - 1994
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1994.tb02090.x
Subject(s) - autophosphorylation , cyclin dependent kinase 9 , mitogen activated protein kinase kinase , map2k7 , cyclin dependent kinase 2 , tropomyosin receptor kinase c , biology , tyrosine kinase , map kinase kinase kinase , biochemistry , proto oncogene tyrosine protein kinase src , cyclin dependent kinase 4 , kinase , microbiology and biotechnology , platelet derived growth factor receptor , protein kinase a , signal transduction , receptor , growth factor
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 μ M . IC 50 values of BE‐23372M for other protein tyrosine kinases, erb B‐2, p43 v‐abl , insulin receptor kinase, and p60 c‐src were 0.42, 1.0, 3.3, and 4.5 μ M , respectively, and the IC 50 for protein kinase C, a serine/threonine kinase, was 4.1 μ M . Cdc2 kinase, casein kinases I and II and cAMP‐dependent protein kinase were not inhibited by 20 μ M 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 μ M 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.