國家衛生研究院 NHRI:Item 3990099045/5790

NHRI > Institute of Biotechnology and Pharmaceutical Research > Weir-Torn Jiaang > Periodical Articles > Item 3990099045/5790

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Title:	Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)
Authors:	Lin, WH;Hsieh, SY;Yen, SC;Chen, CT;Yeh, TK;Hsu, T;Lu, CT;Chen, CP;Chen, CW;Chou, LH;Huang, YL;Cheng, AH;Chang, YI;Tseng, YJ;Yen, KR;Chao, YS;Hsu, JT;Jiaang, WT
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Preclinical investigations and early clinical trial studies suggest that FLT3 inhibitors offer a viable therapy for acute myeloid leukemia. However, early clinical data for direct FLT3 inhibitors provided only modest results because of the failure to fully inhibit FLT3. We have designed and synthesized a novel class of 3-phenyl-1H-5-pyrazolylamine-derived compounds as FLT3 inhibitors which exhibit potent FLT3 inhibition and high selectivity toward different receptor tyrosine kinases. The structure-activity relationships led to the discovery of two series of FLT3 inhibitors, and some potent compounds within these two series exhibited comparable potency to FLT3 inhibitors sorafenib (3) and ABT-869 (4) in both wt-FLT3 enzyme inhibition and FLT3-ITD inhibition on cell growth (MOLM-13 and MV4;11 cells). In particular, the selected compound 12a exhibited the ability to regress tumors in mouse xenograft models using MOLM-13 and MV4;11 cells.
Date:	2011-07
Relation:	Bioorganic and Medicinal Chemistry. 2011 Jul;19(14):4173-4182 .
Link to:	http://dx.doi.org/10.1016/j.bmc.2011.06.016
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0968-0896&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000292301200002 https://www.webofscience.com/wos/woscc/full-record/WOS:000292301200002
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79959956358
Appears in Collections:	[Weir-Torn Jiaang] Periodical Articles [John Tsu-An Hsu] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Chiung-Tong Chen] Periodical Articles

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