Indirubin derivatives as potent FLT3 inhibitors with anti-proliferative activity of acute myeloid leukemic cells.
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 (IC(50)=15 nM) with more than 100-fold selectivity versus 6 other kinases and potent anti-proliferative effect for MV4;11 cells (IC(50)=72 nM) with 30-fold selectivity versus RS4;11 cells. Cell cycle analysis indicated that compound 13 induced cell cycle arrest at G(0)/G(1) phase in MV4;11 cells.
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Soo Jeong
SJ
Choi
Myoung Ju
MJ
Moon
So Deok
SD
Lee
Sang-Un
SU
Choi
Sun-Young
SY
Han
Yong-Chul
YC
Kim
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*
D000903:Antibiotics, Antineoplastic; D007211:Indoles; C027185:indirubin