Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces K562 to differentiate

Blood. 1993 Dec 15;82(12):3524-9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Benzoquinones
  • Catechols / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Cell Line
  • ErbB Receptors / metabolism
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Humans
  • Kinetics
  • Lactams, Macrocyclic
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Mice
  • Molecular Structure
  • Nitriles / pharmacology*
  • Phosphotyrosine
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinones / pharmacology
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Rifabutin / analogs & derivatives
  • Time Factors
  • Tumor Cells, Cultured
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Tyrphostins*

Substances

  • Benzoquinones
  • Catechols
  • Lactams, Macrocyclic
  • Nitriles
  • Quinones
  • Tyrphostins
  • tyrphostin 47
  • tyrphostin AG 568
  • tyrphostin AG 1112
  • Rifabutin
  • Phosphotyrosine
  • Tyrosine
  • herbimycin
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Fusion Proteins, bcr-abl