Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces K562 to differentiate.
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.
Anafi
M
M
Lautenberg Center for Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel.
Gazit
A
A
Zehavi
A
A
Ben-Neriah
Y
Y
Levitzki
A
A
D016475:3T3 Cells; D000818:Animals; D016227:Benzoquinones; D002396:Catechols / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D047029:Lactams, Macrocyclic; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D051379:Mice; D015394:Molecular Structure; D009570:Nitriles / Q000494:pharmacology*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D020032:Tyrphostins
D016227:Benzoquinones; D002396:Catechols; D047029:Lactams, Macrocyclic; D009570:Nitriles; D011809:Quinones; D020032:Tyrphostins; C060152:tyrphostin 47; C084909:tyrphostin AG 568; C084908:tyrphostin AG 1112; D017828:Rifabutin; D019000:Phosphotyrosine; D014443:Tyrosine; C020754:herbimycin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D016044:Fusion Proteins, bcr-abl