Indirubin derivatives as potent FLT3 inhibitors with anti-proliferative activity of acute myeloid leukemic cells |
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Authors: | Soo Jeong Choi Myoung Ju Moon So Deok Lee Sang-Un Choi Sun-Young Han Yong-Chul Kim |
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Institution: | 1. Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea;2. Pharmacology Research Center, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 305-600, Republic of Korea |
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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. |
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