國家衛生研究院 NHRI:Item 3990099045/10552

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shiow-Ju Lee > Periodical Articles > Item 3990099045/10552

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10552

Title:	Design, synthesis, and evaluation of thiazolidine-2,4-dione derivatives as a novel class of glutaminase inhibitors
Authors:	Yeh, TK;Kuo, CC;Lee, YZ;Ke, YY;Chu, KF;Hsu, HY;Chang, HY;Liu, YW;Song, JS;Yang, CW;Lin, LM;Sun, MW;Wu, SH;Kuo, PC;Shih, C;Chen, CT;Tsou, LK;Lee, SJ
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Humans have two glutaminase genes, GLS (GLS1) and GLS2, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for GLS, and the liver isoform (LGA) and glutaminase B (GAB) for GLS2. Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)thiazolidine-2,4- dione (2), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40000 compounds against KGA. Subsequently, a series of thiazolidine-2,4-dione derivatives was synthesized. Most of these were found to inhibit KGA and GAC with comparable activities, were less potent inhibitors of GAB, and were moderately selective for GLS1 over GLS2. The relationships between chemical structure, activity, and selectivity were investigated. The lead compounds obtained were found to (1) offer in vitro cellular activities for inhibiting cell growth, clonogenicity, and cellular glutamate production, (2) exhibit high concentrations of exposure in plasma by a pharmacokinetic study, and (3) reduce the tumor size of xenografted human pancreatic AsPC-1 carcinoma cells in mice.
Date:	2017-07
Relation:	Journal of Medicinal Chemistry. 2017 Jul;60(13):5599-5612.
Link to:	http://dx.doi.org/10.1021/acs.jmedchem.7b00282
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:000405764900022
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85023743600
Appears in Collections:	[Shiow-Ju Lee] Periodical Articles [Lun Kelvin Tsou] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Chuan Shih(2014-2017)] Periodical Articles [Ching-Chuan Kuo] Periodical Articles [Teng-Kuang Yeh] Periodical Articles

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