國家衛生研究院 NHRI:Item 3990099045/5012

NHRI > Institute of Biotechnology and Pharmaceutical Research > Yu-Sheng Chao(2002-2013) > Periodical Articles > Item 3990099045/5012

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5012

Title:	Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein
Authors:	Tsai, TY;Yeh, TK;Chen, X;Hsu, T;Jao, YC;Huang, CH;Song, JS;Huang, YC;Chien, CH;Chiu, JH;Yen, SC;Tang, HK;Chao, YS;Jiaang, WT
Contributors:	Division of Biotechnology and Pharmaceutical Research
Abstract:	Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC(50) of <100 nM with excellent selectivity over DPP-IV, DPP-II, DPP8, and DPP9 (IC(50) > 100 muM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.
Date:	2010-08
Relation:	Journal of Medicinal Chemistry. 2010 Aug;53(18):6572-6583.
Link to:	http://dx.doi.org/10.1021/jm1002556
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000281753700005
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77956717491
Appears in Collections:	[Yu-Sheng Chao(2002-2013)] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Xin Chen(2002-2015)] Periodical Articles [Weir-Torn Jiaang] Periodical Articles

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