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Ba/F3 cells and their use in kinase drug discovery

Warmuth, Markus; Kim, Sungjoon; Gu, Xiang-ju; Xia, Gang; Adrián, Francisco

doi: 10.1097/CCO.0b013e328011a25f
Cancer biology
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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.

Kinase Platform and Department of Lead Discovery, Genomics Institute of the Novartis Research Foundation, San Diego, California, USA

Correspondence to Markus Warmuth, MD, Kinase Platform, Genomics Institute of the Novartis Research Foundation (GNF), 10675 John Jay Hopkins Dr, San Diego, CA 92121, USA E-mail: mwarmuth@gnf.org

© 2007 Lippincott Williams & Wilkins, Inc.