Abstract
We report on the potency of two Tyrphostin tyrosine kinase blockers, AG 1112 and AG 568, to inhibit p210bcr-abl tyrosine kinase activity in K562 cells, concomitant with the induction of erythroid differentiation. AG 568 and especially AG 1112 represent a specific group of nontoxic protein tyrosine kinase blockers among more than 1,400 tested. These compounds possess therapeutic potential for purging Philadelphia chromosome-positive cells in preparation for autologous bone marrow transplantation in chronic myelogenous leukemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Benzoquinones
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Catechols / pharmacology*
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Cell Differentiation / drug effects*
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Cell Division / drug effects
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Cell Line
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ErbB Receptors / metabolism
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Fusion Proteins, bcr-abl / antagonists & inhibitors*
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Humans
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Kinetics
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Lactams, Macrocyclic
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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Mice
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Molecular Structure
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Nitriles / pharmacology*
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Phosphotyrosine
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Quinones / pharmacology
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Receptors, Platelet-Derived Growth Factor / metabolism
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Rifabutin / analogs & derivatives
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Time Factors
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Tumor Cells, Cultured
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Tyrosine / analogs & derivatives
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Tyrosine / analysis
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Tyrphostins*
Substances
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Benzoquinones
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Catechols
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Lactams, Macrocyclic
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Nitriles
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Quinones
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Tyrphostins
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tyrphostin 47
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tyrphostin AG 568
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tyrphostin AG 1112
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Rifabutin
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Phosphotyrosine
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Tyrosine
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herbimycin
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ErbB Receptors
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Protein-Tyrosine Kinases
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Receptors, Platelet-Derived Growth Factor
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Fusion Proteins, bcr-abl