358 Study of cetuximab and panitumumab activity in an 80 cell line panel to evaluate specificity of small molecule EGFR inhibitors

Abstract

Indirubin derivatives were identified as potent FLT3 tyrosine kinase inhibitors with anti-proliferative activity at acute myeloid leukemic cell lines, RS4;11 and MV4;11 which express FLT3-WT and FLT3-ITD mutation, respectively. Among several 5 and 5′-substituted indirubin derivatives, 5-fluoro analog, 13 exhibited potent inhibitory activity at FLT3 (IC50 = 15 nM) with more than 100-fold selectivity versus 6 other kinases and potent anti-proliferative effect for MV4;11 cells (IC50 = 72 nM) with 30-fold selectivity versus RS4;11 cells. Cell cycle analysis indicated that compound 13 induced cell cycle arrest at G0/G1 phase in MV4;11 cells.