Abstract C200: Effects of indirubin derivatives on the FLT3 activity and growth of acute myeloid leukemia cell lines

Indirubin is an active constituent of traditional Chinese recipe used for the treatment of chronic myelocytic leukemia. In this study, inhibitory activity of indirubin and its derivatives toward Fms‐like tyrosine kinase 3 (FLT3) was examined. Indirubin‐3′‐oxime(IO) and 6‐bromoindirubin‐3′‐oxime(BIO) showed potent inhibitory activity against FLT3 with 50% inhibitory concentration (IC50) of 79 nM and 254 nM, respectively. Meanwhile, indirubin and 6‐bromoindirubin exhibited negligible effect on FLT3 inhibitory activity up to 10 µM. We also tested the cytotoxicity of those compounds against acute myeloid leukemia cell lines; MV4;11 cells harboring constitutively activated form of FLT3 and RS4;11 cells with wild type FLT3. IO and BIO potently inhibited the growth of MV4;11 cells with IC50 of 30 nM and 61 nM, respectively. On the other hand, RS4;11 cells were far less sensitive to those compounds with IC50 values of 3600 nM and 820 nM, respectively. In the cell cycle assay, IO arrested the cell cycle of MV4;11 cells at G1 phase, and increased dead cell population at sub‐G1 phase about 25 and 50% at 0.1 and 1.0 µM after 48 hours, respectively. These results strongly suggest that the derivatives of IO have potentials to be developed for novel anti‐leukemic agents. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C200.