Design, Synthesis, and Biological Evaluation of HDAC Degraders with CRBN E3 Ligase Ligands
文献类型：期刊论文
| 作者 | Lu, Yingxin2; Sun, Danwen1; Xiao, Donghuai2; Shao, Yingying1; Su, Mingbo1; Zhou, Yubo1 ; Li, Jia1; Zhu, Shulei2; Lu, Wei2
|
| 刊名 | MOLECULES
 |
| 出版日期 | 2021-12-01 |
| 卷号 | 26期号:23页码:19 |
| 关键词 | HDAC degraders CRBN ligands proteins of interest benzyl alcohol linkage |
| DOI | 10.3390/molecules26237241 |
| 通讯作者 | Li, Jia(jli@simm.ac.cn) ; Zhu, Shulei(slzhu@chem.ecnu.edu.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn) |
| 英文摘要 | Histone deacetylases (HDACs) play important roles in cell growth, cell differentiation, cell apoptosis, and many other cellular processes. The inhibition of different classes of HDACs has been shown to be closely related to the therapy of cancers and other diseases. In this study, a series of novel CRBN-recruiting HDAC PROTACs were designed and synthesized by linking hydroxamic acid and benzamide with lenalidomide, pomalidomide, and CC-220 through linkers of different lengths and types. One of these PROTACs, denoted 21a, with a new benzyl alcohol linker, exhibited comparably excellent HDAC inhibition activity on different HDAC classes, acceptable degradative activity, and even better in vitro anti-proliferative activities on the MM.1S cell line compared with SAHA. Moreover, we report for the first time the benzyl alcohol linker, which could also offer the potential to be used to develop more types of potent PROTACs for targeting more proteins of interest (POI). |
| WOS关键词 | DEGRADATION ; INHIBITORS |
| 资助项目 | Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China[22077034] ; National Natural Science Foundation of China[82104000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000734514000001 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300818]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Jia; Zhu, Shulei; Lu, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, 189 Guo Shoujing Rd, Shanghai 201203, Peoples R China 2.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lu, Yingxin,Sun, Danwen,Xiao, Donghuai,et al. Design, Synthesis, and Biological Evaluation of HDAC Degraders with CRBN E3 Ligase Ligands[J]. MOLECULES,2021,26(23):19. |
| APA | Lu, Yingxin.,Sun, Danwen.,Xiao, Donghuai.,Shao, Yingying.,Su, Mingbo.,...&Lu, Wei.(2021).Design, Synthesis, and Biological Evaluation of HDAC Degraders with CRBN E3 Ligase Ligands.MOLECULES,26(23),19. |
| MLA | Lu, Yingxin,et al."Design, Synthesis, and Biological Evaluation of HDAC Degraders with CRBN E3 Ligase Ligands".MOLECULES 26.23(2021):19. |
入库方式： OAI收割
来源：上海药物研究所
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