Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors
文献类型：期刊论文
| 作者 | Xu, Xi1,2; Kuang, Zijian1; Han, Jie2; Meng, Ying1; Li, Lei1; Luan, Hongyu1; Xu, Pengfei1; Wang, Jubo1; Luo, Cheng2 ; Ding, Hong2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2019-11-14 |
| 卷号 | 62期号:21页码:9642-9657 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.9b01035 |
| 文献子类 | Article |
| 英文摘要 | Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Because of its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast, and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors. |
| WOS关键词 | KIDNEY-TYPE GLUTAMINASE ; POLARIZATION ASSAY ; METABOLISM ; DESIGN ; SUPPRESSION ; EXPRESSION ; MECHANISM ; GROWTH |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000497260700017 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309420]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Zhiyu; Bian, Jinlei |
| 作者单位 | 1.China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Tongjiaxiang 24, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Xi,Kuang, Zijian,Han, Jie,et al. Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2019,62(21):9642-9657. |
| APA | Xu, Xi.,Kuang, Zijian.,Han, Jie.,Meng, Ying.,Li, Lei.,...&Bian, Jinlei.(2019).Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,62(21),9642-9657. |
| MLA | Xu, Xi,et al."Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 62.21(2019):9642-9657. |
入库方式： OAI收割
来源：上海药物研究所
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