國家衛生研究院 NHRI:Item 3990099045/8768

NHRI > Institute of Biotechnology and Pharmaceutical Research > Weir-Torn Jiaang > Periodical Articles > Item 3990099045/8768

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8768

Title:	Identification of a potent 5-phenyl-thiazol-2-ylamine-based inhibitor of FLT3 with activity against drug resistance-conferring point mutations
Authors:	Chen, CT;Hsu, JTA;Lin, WH;Lu, CT;Yen, SC;Hsu, T;Huang, YL;Song, JS;Chen, CH;Chou, LH;Yen, KJ;Chen, CP;Kuo, PC;Huang, CL;Eugene Liu, H;Chao, YS;Yeh, TK;Jiaang, WT
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Numerous FLT3 inhibitors have been explored as a viable therapy for the treatment of acute myeloid leukemia (AML). However, clinical data have been underwhelming due to incomplete inhibition of FLT3 or the emergence of resistant mutations treated with these older agents. We previously developed a series of 3-phenyl-1H-5-pyrazolylamine derivatives as highly potent and selective FLT3 inhibitors with good in vivo efficacy using an intravenous (IV) route. However, the poor bioavailability of these pyrazole compounds limits the development of these promising antileukemic compounds for clinical use. Herein, we describe a novel class of 5-phenyl-thiazol-2-ylamine compounds that are multi-targeted FLT3 inhibitors. From this class of compounds, compound 7h was very potent against AML cell lines and exhibited excellent oral efficacy in AML xenograft models. In addition, further studies demonstrated that compound 7h exhibited potent in vitro and in vivo activities against clinically relevant AC220 (3)-resistant kinase domain mutants of FLT3-ITD.
Date:	2015-07
Relation:	European Journal of Medicinal Chemistry. 2015 Jul;100:151-161.
Link to:	http://dx.doi.org/10.1016/j.ejmech.2015.05.008
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000358097200016
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84931264115
Appears in Collections:	[Weir-Torn Jiaang] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles [John Tsu-An Hsu] Periodical Articles [Chiung-Tong Chen] Periodical Articles

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