Tyrphostin induced growth inhibition : correlation with effect on p210bcr-abl autokinase activity in K562 chronic myelogenous leukemia

摘要: We have examined a series of tyrosine kinase inhibitors structurally related to erbstatin (tyrphostins) for inhibition p210bcr-abl autokinase activity in vitro and growth chronic myelogenous leukemia (CML)K562 cells. Of the tyrphostins with IC50 < 50 microM, AG814, AG946, AG952, AG896, AG953, AG956 AG957 (structurally lavendustin A piceatannol) completely inhibited an immune complex assay. Another group (AG807, AG568, AG763, AG1076, AG490, AG1318, AG556, AG1319, AG555 AG1111) inhibits K562 cells but not activity. compounds which inhibit activity, DNA synthesis as early 2 h (60% at 20 microM AG957), time concentration drug where RNA protein were affected. phosphorylation living by 1 without total phosphorylation. Growth was reversible after 4 exposure, irreversible 24 h. can be considered important lead structure development anti-bcr-abl antagonists. These data also raise possibility that bcr-abl is directly linked maintenance Philadelphia chromosome positive (Ph+) CML