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http://ir.nhri.org.tw/handle/3990099045/10552
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| 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: | [李秀珠] 期刊論文
[鄒倫] 期刊論文
[陳炯東] 期刊論文
[石全(2014-2017)] 期刊論文
[郭靜娟] 期刊論文
[葉燈光] 期刊論文
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| PUB28609101.pdf | | 7104Kb | Adobe PDF | 478 | View/Open |
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