Discovery and characterization of a novel glucose-6-phosphate dehydrogenase (G6PD) inhibitor via high-throughput screening
文献类型：期刊论文
| 作者 | Luo, Zhongyuan1,2; Du, Daohai1,2; Liu, Yanjun2; Lu, Tian2; Liu, Liping2; Jiang, Hualiang2 ; Chen, Kaixian2; Shan, Changliang3,4; Luo, Cheng1,2,5
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2021 |
| 卷号 | 40页码:127905 |
| 关键词 | Glucose-6-phosphate dehydrogenase inhibitor High-throughput screening Enzyme kinetics assay Absorption photometry assay |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2021.127905 |
| 文献子类 | Article |
| 英文摘要 | Altered glucose-6-phosphate dehydrogenase (G6PD) status is influential in many cellular pathophysiological processes and diseases, making G6PD a potential target for cancer therapy. However, the available G6PD inhibitors are very limited and restricted. Here we developed a reducing equivalent nicotinamide adenine dinucleotide phosphate (NADPH) absorption photometry assay based on enzyme kinetics to characterize G6PD activity. In this way, we performed a high-throughput screening (HTS) to an in house library. And then we identified compound named Wedelolactone inhibiting G6PD strongly in a non-competitive, reversible way. In addition, we did the surface Plasmon Resonance (SPR) assay and indicated the K-D between Wedelolactone and G6PD protein was 3.64 mu M. Furthermore, our basic colony formation assay showed the inhibitory effect of Wedelolactone on the proliferation of ovarian cancer cells (IC50 similar to 10 mu M). Thus, we provided a high-throughput screening assay to quickly and efficiently discover G6PD inhibitors, and identified Wedelolactone as a G6PD inhibitor, implying that Wedelolactone suppresses ovarian cancer partly through targeting G6PD. |
| WOS关键词 | PENTOSE-PHOSPHATE PATHWAY ; C-SRC ; CANCER ; DEHYDROEPIANDROSTERONE ; NADPH |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000657395500005 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309393]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shan, Changliang; Luo, Cheng |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr,Ctr Chem Biol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Nankai Univ, State Key Lab Med Chem Biol, Coll Pharm, Tianjin 300350, Peoples R China; 4.Nankai Univ, Tianjin Key Lab Mol Drug Res, Tianjin 300350, Peoples R China; 5.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Zhongyuan,Du, Daohai,Liu, Yanjun,et al. Discovery and characterization of a novel glucose-6-phosphate dehydrogenase (G6PD) inhibitor via high-throughput screening[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2021,40:127905. |
| APA | Luo, Zhongyuan.,Du, Daohai.,Liu, Yanjun.,Lu, Tian.,Liu, Liping.,...&Luo, Cheng.(2021).Discovery and characterization of a novel glucose-6-phosphate dehydrogenase (G6PD) inhibitor via high-throughput screening.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,40,127905. |
| MLA | Luo, Zhongyuan,et al."Discovery and characterization of a novel glucose-6-phosphate dehydrogenase (G6PD) inhibitor via high-throughput screening".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 40(2021):127905. |
入库方式： OAI收割
来源：上海药物研究所
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