title: Ba/F3 cells and their use in kinase drug discovery.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kinase Platform and Department of Lead Discovery, Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. mwarmuth@gnf.org
authors.forename: Markus
authors.initials: M
authors.lastname: Warmuth
authors.forename: Sungjoon
authors.initials: S
authors.lastname: Kim
authors.forename: Xiang-ju
authors.initials: XJ
authors.lastname: Gu
authors.forename: Gang
authors.initials: G
authors.lastname: Xia
authors.forename: Francisco
authors.initials: F
authors.lastname: Adrián
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors