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BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML.

Authors: Lin, WH  Jiaang, WT  Chen, CW  Yen, KJ  Hsieh, SY  Yen, SC  Chen, CP  Chang, KY  Chang, CY  Chang, TY  Huang, YL  Yeh, TK  Chao, YS  Chen, CT  Hsu, JT 
Citation: Lin WH, etal., Br J Cancer. 2012 Jan 31;106(3):475-81. doi: 10.1038/bjc.2011.564. Epub 2011 Dec 20.
Pubmed: (View Article at PubMed) PMID:22187040
DOI: Full-text: DOI:10.1038/bjc.2011.564

BACKGROUND: Activating mutations of Fms-like tyrosine kinase 3 (FLT3) constitute a major driver in the pathogenesis of acute myeloid leukaemia (AML). Hence, pharmacological inhibitors of FLT3 are of therapeutic interest for AML. METHODS: The effects of inhibition of FLT3 activity by a novel potent FLT3 inhibitor, BPR1J-097, were investigated using in vitro and in vivo assays. RESULTS: The 50% inhibitory concentration (IC(50)) of BPR1J-097 required to inhibit FLT3 kinase activity ranged from 1 to 10 nM, and the 50% growth inhibition concentrations (GC(50)s) were 21+/-7 and 46+/-14 nM for MOLM-13 and MV4-11 cells, respectively. BPR1J-097 inhibited FLT3/signal transducer and activator of transcription 5 phosphorylation and triggered apoptosis in FLT3-driven AML cells. BPR1J-097 also showed favourable pharmacokinetic property and pronounced dose-dependent tumour growth inhibition and regression in FLT3-driven AML murine xenograft models. CONCLUSION: These results indicate that BPR1J-097 is a novel small molecule FLT-3 inhibitor with promising in vivo anti-tumour activities and suggest that BPR1J-097 may be further developed in preclinical and clinical studies as therapeutics in AML treatments.

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CRRD Object Information
CRRD ID: 11049503
Created: 2016-04-07
Species: All species
Last Modified: 2016-04-07
Status: ACTIVE



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