Activity of FB2, a novel dual Abl/Src tyrosine kinase inhibitor, against imatinib-resistant chronic myeloid leukemia in vivo and in vitro.

Abstract

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.

• Authors: He Liu, Hongyan Li, Zhiqiang Feng, Jun Tai, Yang Meng, Hongbo Wang, Hongqi Xin, Sen Zhang, Mingxin Zuo, Yan Zhang, Xiaoguang Chen
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 50 Issue 3 Pg. 437-46 (Mar 2009) ISSN: 1029-2403 [Electronic] United States
• PMID: 19347730 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Proto-Oncogene Proteins c-abl
• src-Family Kinases

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Benzamides
• Drug Resistance, Neoplasm
• Humans
• Imatinib Mesylate
• K562 Cells
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
• Mice
• Mice, SCID
• Phosphorylation (drug effects)
• Piperazines (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-abl (antagonists & inhibitors)
• Pyrimidines (pharmacology)
• Survival Rate
• Xenograft Model Antitumor Assays
• src-Family Kinases (antagonists & inhibitors)