Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371961 | Bioorganic & Medicinal Chemistry Letters | 2010 | 5 Pages |
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.
Graphical abstract5-Fluoro-indirubin-3′-oxime, 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.Figure optionsDownload full-size imageDownload as PowerPoint slide