Effects of herbimycin A derivatives on growth and differentiation of K562 human leukemic cells.

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.