Activity of FB2, a novel dual Abl/Src tyrosine kinase inhibitor, against imatinib-resistant chronic myeloid leukemia in vivo and in vitro.
FB2 is a novel Abl/Src dual tyrosine kinase inhibitor which is designed to overcome imatinib resistance. Besides imatinib-sensitive cell lines (K562), FB2 significantly inhibited the growth of imatinib-resistant cell lines of different resistance mechanisms (K562/G5.0 and K562/G01), and decreased the expression of autophosphorylation of Bcr/Abl, c-Src and Lyn kinases on them. It also inhibited the proliferation of Src over activated cells DU145 and MDA-MB-231. Furthermore, FB2 potently prolonged the survival time of non-obese diabetic/severe combined immunodeficient mice harboured K562/G5.0 cells. These results indicated that FB2, an Abl/Src dual tyrosine kinase inhibitor, is a promising candidate for imatinib-resistant CML and Src over activated cancer.
Liu
He
H
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Li
Hongyan
H
Feng
Zhiqiang
Z
Tai
Jun
J
Meng
Yang
Y
Wang
Hongbo
H
Xin
Hongqi
H
Zhang
Sen
S
Zuo
Mingxin
M
Zhang
Yan
Y
Chen
Xiaoguang
X
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases