Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors
文献类型：期刊论文
| 作者 | Ji, Yue-Yang4; Lin, Sen-Dong4; Wang, Yu-Jie1; Su, Ming-Bo1; Zhang, Wei4; Gunosewoyo, Hendra3; Yang, Fan4; Li, Jia1 ; Tang, Jie2; Zhou, Yu-Bo1
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2017-12-01 |
| 卷号 | 141页码:101-112 |
| 关键词 | Tranylcypromine LSD1 Stereoselective cyclopropanation Chiral synthesis MAO-A MAO-B |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2017.09.073 |
| 文献子类 | Article |
| 英文摘要 | Aberrant expression of lysine specific histone demethylase I (ISM) has been increasingly associated with numerous cancer cells and several proof-of-concept studies are strongly suggestive of its potential as a druggable target. Tranylcypromine (TCP) is an antidepressant originally known to target the monoamine oxidases A and B (MAO-A and MAO-B), which are structurally related to LSD1. A number of TCP derivatives have been identified as potent LSDI inhibitors, with a handful of them currently being tested in clinical trials. However, thus far the majority of structure-activity relationship studies reported on these TCP derivatives have been mostly limited to the racemates. In this study, we present the SAR data for a novel series of conformationally-restricted TCP-based LSD1 inhibitors, both in their racemic and enantiomerically pure forms. Compounds 18b and 19b were identified as the most potent LSD1 inhibitors within this series, possessing excellent selectivity (> 10,000-fold) against MAO-A and MAO-B. These compounds activated CD86 expression on the human MV4-11 AML cells following 10 days of exposure, accompanied with the apparent cytotoxicity. Taken together, these findings are consistent with the pharmacological inhibition of LSDI and further provide structural insights on the binding modes of these TCP derivatives and their enantiomers at the LSDI. (C) 2017 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | ACUTE MYELOID-LEUKEMIA ; STEM-CELLS ; PHARMACOLOGICAL INHIBITION ; STRUCTURAL BASIS ; CANCER-THERAPY ; TRANS-2-PHENYLCYCLOPROPYLAMINE ; CONSTRUCTION ; MAINTENANCE ; METHYLATION ; EXPRESSION |
| 资助项目 | Chinese Academy of Sciences[XDA12020313] ; National Natural Science Foundation of China[81703544] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000417962900010 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272363]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Zhou, Yu-Bo; Yu, Li-Fang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China; 2.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 3.Curtin Univ, Fac Hlth Sci, Sch Pharm, Perth, WA 6102, Australia; 4.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Ji, Yue-Yang,Lin, Sen-Dong,Wang, Yu-Jie,et al. Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,141:101-112. |
| APA | Ji, Yue-Yang.,Lin, Sen-Dong.,Wang, Yu-Jie.,Su, Ming-Bo.,Zhang, Wei.,...&Yu, Li-Fang.(2017).Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,141,101-112. |
| MLA | Ji, Yue-Yang,et al."Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 141(2017):101-112. |
入库方式： OAI收割
来源：上海药物研究所
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