Tanaka S, Okabe T, Chieda S, Endo K, Kanoh T, Okura A, Yoshida E
Banyu Tsukuba Research Institute, Merck Research Laboratories, Tsukuba.
Jpn J Cancer Res. 1994 Mar;85(3):253-9. doi: 10.1111/j.1349-7006.1994.tb02090.x.
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.
真菌代谢产物BE - 23372M是一种结构新颖的蛋白激酶抑制剂。其对表皮生长因子（EGF）受体激酶的IC50为0.03微摩尔。BE - 23372M对其他蛋白酪氨酸激酶erbB - 2、p43v - abl、胰岛素受体激酶和p60c - src的IC50值分别为0.42、1.0、3.3和4.5微摩尔，而对丝氨酸/苏氨酸激酶蛋白激酶C的IC50为4.1微摩尔。20微摩尔的BE - 23372M对细胞周期蛋白依赖性激酶2（Cdc2激酶）、酪蛋白激酶I和II以及环磷酸腺苷（cAMP）依赖性蛋白激酶没有抑制作用。动力学研究表明，BE - 23372M在底物肽和三磷酸腺苷（ATP）方面具有竞争性。0.1微摩尔的BE - 23372M能明显抑制可溶性EGF受体激酶的自身磷酸化。A431细胞中EGF受体的自身磷酸化也受到抑制。这些结果表明，BE - 23372M是一种强效且特异性的EGF受体激酶抑制剂。它应是EGF受体激酶研究的一个有价值的工具。
