Honma Y, Kasukabe T, Hozumi M, Shibata K, Omura S
Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina-machi, Japan.
Anticancer Res. 1992 Jan-Feb;12(1):189-92.
Herbimycin A, a specific tyrosine kinase inhibitor, induced erythroid differentiation of human myelogenous leukemia K562 cells with a high level of bcr/abl tyrosine kinase. Several derivatives of herbimycin A were synthesized and their effects on cell proliferation and differentiation of K562 cells were examined. Of the compounds tested, 19-allylaminoherbimycin A was the most effective in inducing differentiation of K562 cells. However, the parent compound was the most potent growth inhibitor, suggesting that chemical modification of herbimycin A reduces the growth-inhibiting activity. The sensitivities of K562 cells to herbimycin derivatives were different from those of a rat kidney cell line infected with Rous sarcoma virus (v-src), suggesting that bcr/abl kinase may differ in sensitivity from other tyrosine kinases. These results indicate that a specific inhibitor of bcr/abl kinase could be an effective antitumor agent against chronic myelogenous leukemia.
除草菌素A是一种特异性酪氨酸激酶抑制剂，可诱导具有高水平bcr/abl酪氨酸激酶的人髓性白血病K562细胞向红系分化。合成了除草菌素A的几种衍生物，并检测了它们对K562细胞增殖和分化的影响。在所测试的化合物中，19-烯丙基氨基除草菌素A在诱导K562细胞分化方面最有效。然而，母体化合物是最有效的生长抑制剂，这表明除草菌素A的化学修饰降低了其生长抑制活性。K562细胞对除草菌素衍生物的敏感性与感染劳氏肉瘤病毒（v-src）的大鼠肾细胞系不同，这表明bcr/abl激酶的敏感性可能与其他酪氨酸激酶不同。这些结果表明，bcr/abl激酶的特异性抑制剂可能是一种有效的抗慢性髓性白血病的抗肿瘤药物。
