Discovery of Novel Long-Chain Alkenyl Diacid Derivatives as ACLY Inhibitors
文献类型：期刊论文
| 作者 | Song, Gao-Lei2,3; Cao, Lei3; Zhang, Mei3 ; Yang, Yu-Rou2,3; Ma, Jie3; Xie, Zhi-Fu3; Li, Jing-Ya3; Nan, Fa-Jun1,2,3
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| 刊名 | CHINESE JOURNAL OF CHEMISTRY
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| 出版日期 | 2022-08-29 |
| 页码 | 8 |
| 关键词 | Alkenyl diacid derivatives Cancer ACLY inhibitors Acetyl-CoA Structure-activity relationships |
| ISSN号 | 1001-604X |
| DOI | 10.1002/cjoc.202200362 |
| 通讯作者 | Li, Jing-Ya() ; Nan, Fa-Jun(fjnan@simm.ac.cn) |
| 英文摘要 | Comprehensive Summary ATP citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein acetylation. The aberrant expression and activity of ACLY has been documented in multiple human cancers. ETC-1002 is an indirect ACLY inhibitor, and it has recently been approved by the FDA as an additional therapeutic option in high-risk hypercholesterolemia patients unable to meet goals with standard therapy. In this work, we identified a series of novel long-chain alkenyl diacids as potent direct ACLY inhibitors, and comprehensive structure-activity relationship analysis showed that compound 18f was the most potent ACLY inhibitor with an IC50 value of 1.5 mu mol/L. Subsequent ester formation of 18f gave a new series of compounds such as 25f that maintained ACLY inhibitory activity and improved antitumor cell proliferation effects. |
| WOS关键词 | ATP-CITRATE LYASE ; EPIGENETICS |
| 资助项目 | Personalized Medicines-Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040328] ; Medical Guidance Project of Shanghai Science and Technology Commission[20S11903400] ; Natural Science Foundation of Shanghai[21ZR1475300] ; National Natural Science Foundation of China[82170872] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000847230200001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302111]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Jing-Ya; Nan, Fa-Jun |
| 作者单位 | 1.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, Gao-Lei,Cao, Lei,Zhang, Mei,et al. Discovery of Novel Long-Chain Alkenyl Diacid Derivatives as ACLY Inhibitors[J]. CHINESE JOURNAL OF CHEMISTRY,2022:8. |
| APA | Song, Gao-Lei.,Cao, Lei.,Zhang, Mei.,Yang, Yu-Rou.,Ma, Jie.,...&Nan, Fa-Jun.(2022).Discovery of Novel Long-Chain Alkenyl Diacid Derivatives as ACLY Inhibitors.CHINESE JOURNAL OF CHEMISTRY,8. |
| MLA | Song, Gao-Lei,et al."Discovery of Novel Long-Chain Alkenyl Diacid Derivatives as ACLY Inhibitors".CHINESE JOURNAL OF CHEMISTRY (2022):8. |
入库方式： OAI收割
来源：上海药物研究所
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