Hybrid compounds as new Bcr/Abl inhibitors

Deping Wang; Zhang Zhang; Xiaoyun Lu; Yubing Feng; Kun Luo; Jirong Gan; Liu Yingxue; Junting Wan; Xiang Li; Fengxiang Zhang; Zhengchao Tu; Qian Cai; Xiaomei Ren; Ke Ding

doi:10.1016/j.bmcl.2011.02.029

Hybrid compounds as new Bcr/Abl inhibitors

Bioorg Med Chem Lett. 2011 Apr 1;21(7):1965-8. doi: 10.1016/j.bmcl.2011.02.029. Epub 2011 Feb 13.

Authors

Deping Wang¹, Zhang Zhang, Xiaoyun Lu, Yubing Feng, Kun Luo, Jirong Gan, Liu Yingxue, Junting Wan, Xiang Li, Fengxiang Zhang, Zhengchao Tu, Qian Cai, Xiaomei Ren, Ke Ding

Affiliation

¹ Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No 190, Kaiyuan Avenue, Science Park, Guangzhou 510530, China.

PMID: 21376587
DOI: 10.1016/j.bmcl.2011.02.029

Abstract

A series of 2,4-disubstituted thiazole derivatives were designed and synthesized as new Bcr/Abl inhibitors by hybriding the structural moieties from FDA approved imatinib, nilotinib and dasatinib. The new inhibitors strongly suppressed the activity of Bcr/Abl kinase and potently inhibited the proliferation of K562 and KU812 leukemia cancer cells. Compound 4i displayed comparable potency with that of nilotinib in both biochemical kinase assay and cancer cell growth inhibition assay. These inhibitors might serve as lead compounds for further developing new anticancer drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Drug Screening Assays, Antitumor
Fusion Proteins, bcr-abl / antagonists & inhibitors*
Humans
Leukemia / pathology
Models, Molecular
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Thiazoles
Fusion Proteins, bcr-abl