Yeh, Teng-Kuang Kuo, Ching-Chuan Lee, Yue-Zhi Ke, Yi-Yu Chu, Kuang-Feng Hsu, Hsing-Yu Chang, Hsin-Yu Liu, Yu-Wei Song, Jen-Shin Yang, Cheng-Wei Lin, Li-Mei Sun, Manwu Wu, Szu-Huei Kuo, Po-Chu Shih, Chuan Chen, Chiung-Tong Tsou, Lun Kelvin Lee, Shiow-Ju Design, Synthesis, and Evaluation of Thiazolidine-2,4-dione Derivatives as a Novel Class of Glutaminase Inhibitors Humans have two glutaminase genes, <i>GLS</i> (<i>GLS1</i>) and <i>GLS2</i>, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for <i>GLS</i>, and the liver isoform (LGA) and glutaminase B (GAB) for <i>GLS2</i>. Initial hit compound (<i>Z</i>)-5-((1-(4-bromophenyl)-2,5-dimethyl-1<i>H</i>-pyrrol-3-yl)­methylene)­thiazolidine-2,4-dione (<b>2</b>), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40 000 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. GLS 1;GLS 2;Glutaminase Inhibitors Humans;LGA;glutaminase;GAC;GAB;40 000 compounds;KGA 2017-06-13
    https://acs.figshare.com/articles/dataset/Design_Synthesis_and_Evaluation_of_Thiazolidine-2_4-dione_Derivatives_as_a_Novel_Class_of_Glutaminase_Inhibitors/5155777
10.1021/acs.jmedchem.7b00282.s002