Abstract 6207: Ba/F3 kinase mutant cell panel, a powerful cell model for the discovery and development of inhibitors for kinase specific mutation

Cancer Research(2022)

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摘要
Abstract Although over 70 protein kinase inhibitors have been approved by FDA since 2001, the protein kinase is still the hot target class of molecularly targeted cancer therapy because of the discovery of new driver kinase fusion mutation and a large number of secondary kinase mutations after the inhibitor treatment in cancer patients with the sequencing technology advancement, the need for new generation specific small molecule kinase inhibitors is still unmet, and it urge the industry to development more accurate, efficient kinase cellular assay models.Ba/F3 line is a popular cell model because many protein kinases and their mutants can transform the Ba/F3 cells to be growth independent of exogenous IL-3 supplement, while their inhibitors can antagonize these effects. Our group have generated a large of cell line panel with over 300 different well validated (sequencing, Western Blot and inhibitor test) Ba/F3 kinase cell lines for kinase inhibitor screening and development, covering several hot kinases, such as EGFR, EML-ALK, FLT3, NTRK, ROS1, HER, BCR-ABL, RET, FGFR1, FGFR2, FGFR3, FGFR4, KRAS, cMET, et al. Except used in in vitro high-throughput compound screening, most of the transformed Ba/F3 lines can grow well in immune-deficient mice and were also used to evaluate the efficacy of drug candidate and its downstream signaling in vivo. Our data indicate that our Ba/F3 cell line panel is a powerful cell model for new kinase inhibitor discovery and development. Citation Format: Yu Wang, Yao Peng, Yao Tang, Lin Zhou, Jinying Ning, Feng Hao. Ba/F3 kinase mutant cell panel, a powerful cell model for the discovery and development of inhibitors for kinase specific mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6207.
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关键词
ba/f3 kinase,mutant cell panel,specific mutation,inhibitors
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