Title:Research Status, Synthesis and Clinical Application of Recently
Marketed and Clinical BCR-ABL Inhibitors
Volume: 29
Issue: 17
Author(s): Xiao-Liang Xu, Yu-Jing Cao , Wen Zhang and Guo-Wu Rao *
Affiliation:
- College of Pharmaceutical Science, Zhejiang University of Technology, and Institute of Drug Development
& Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, P.R. China
Keywords:
Chronic myelogenous leukemia (CML), BCR-ABL, tyrosine kinase inhibitors (TKIs), research status, synthesis, clinical applications.
Abstract: Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in
cell proliferation, adhesion, and survival properties, which are the main causes of chronic
myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has
become one of the effective methods for the treatment of chronic myelogenous leukemia.
Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors
(TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the
emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed
strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib
were able to overcome most of the mutation resistance but not T315I mutations. Therefore,
in order to further overcome the problem of drug resistance, new types of KTIs such
as flumatinib and radotinib have been developed, providing more options for clinical
treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL
inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been
introduced into the clinical market in recent years. We reviewed their research status, synthesis
methods, and clinical applications.
