國家衛生研究院 NHRI:Item 3990099045/6175

NHRI > Institute of Biotechnology and Pharmaceutical Research > John Tsu-An Hsu > Periodical Articles > Item 3990099045/6175

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6175

Title:	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
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	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.
Date:	2012-01
Relation:	British Journal of Cancer. 2012 Jan;106(3):475-481.
Link to:	http://dx.doi.org/10.1038/bjc.2011.564
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0007-0920&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000300302300008
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84856409052
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Weir-Torn Jiaang] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles

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