Ba/F3 cells and their use in kinase drug discovery

被引:186
作者
Warmuth, Markus
Kim, Sungjoon
Gu, Xiang-ju
Xia, Gang
Adrian, Francisco
机构
[1] Novartis Res Fdn, Kinase Platform, Genom Inst, San Diego, CA 92121 USA
[2] Novartis Res Fdn, Dept Lead Discovery, Genom Inst, San Diego, CA 92121 USA
关键词
cancer; high-throughput cellular profiling; inhibitor resistance; kinase; small-molecule kinase inhibitor;
D O I
10.1097/CCO.0b013e328011a25f
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review Due to their ability to function as dominant oncogenes, protein kinases have become favored targets in the quest for 'molecularly-targeted' cancer chemotherapeutics. The discovery of a large number of cancer-associated mutations in the kinome, and the progress in developing specific small-molecule kinase inhibitors has increased the need for accurate, reproducible, and efficient kinase activity-dependent cellular assay systems. Recent findings Ba/F3, a murine interleukin-3 dependent pro-B cell line is increasingly popular as a model system for assessing both the potency and downstream signaling of kinase oncogenes, and the ability of small-molecule kinase inhibitors to block kinase activity. Facilitated by their growth properties, Ba/F3 cells have recently been adapted to high-throughput assay formats for compound profiling. Further, several published approaches show promise in predicting resistance to small-molecule kinase inhibitors elicited by point mutations interfering with inhibitor binding. Summary Ba/F3 cells are an increasingly popular tool in kinase drug discovery. The ability to test the transforming capacity of newly identified kinase mutations, and to profile drug candidates and compound libraries in high-throughput fashion, combined with the use of Ba/F3 cells to predict clinical resistance will greatly facilitate developments in this field.
引用
收藏
页码:55 / 60
页数:6
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