Discovery of HyT-Based Degraders of CDK9-Cyclin T1 Complex
文献类型：期刊论文
| 作者 | Lin, Rongkun2; Yang, Jie1; Liu, Ting2; Wang, Mingyu3,4; Ke, Chongrong7; Luo, Cheng2,3,4,5,6 ; Lin, Jin2; Li, Jiacheng3,4; Lin, Hua1
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| 刊名 | CHEMISTRY & BIODIVERSITY
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| 出版日期 | 2023-07-13 |
| 页码 | 10 |
| ISSN号 | 1612-1872 |
| 关键词 | CDK9 cyclin T1 degrader hydrophobic tag protein degradation |
| DOI | 10.1002/cbdv.202300769 |
| 通讯作者 | Lin, Jin(linjinscu@fjmu.edu.cn) ; Li, Jiacheng(201728012342073@simm.ac.cn) ; Lin, Hua(hlin@fjnu.edu.cn) |
| 英文摘要 | Direct modulation of the non-kinase functions of cyclin and CDK-cyclin complexes poses challenges. We utilize hydrophobic tag (HyT) based small-molecule degraders induced degradation of cyclin T1 and its corresponding kinase partner CDK9. LL-CDK9-12 demonstrated the most potent and selective degradation ability, with DC50 values of 0.362 & mu;M against CDK9 and 0.680 & mu;M against cyclin T1. In prostate cancer cells, LL-CDK9-12 showed enhanced anti-proliferative activity than its parental molecule SNS032 and LL-K9-3, the previous reported CDK9-cyclin T1 degrader. Moreover, LL-CDK9-12 suppressed the downstream signaling of CDK9 and AR efficiently. Altogether, LL-CDK9-12 was an effective dual degrader of CDK9-cyclin T1 and helped study the unknown function of CDK9-cyclin T1. These results suggest that HyT-based degraders could be used as a strategy to induce the degradation of protein complexes, providing insights for the design of protein complexes & PRIME; degraders. |
| WOS关键词 | TAGGING-MEDIATED DEGRADATION ; TARGETED PROTEIN-DEGRADATION ; SELECTIVE-INHIBITION ; ANDROGEN RECEPTOR ; CANCER ; CDK9 ; TRANSCRIPTION ; POTENT |
| 资助项目 | Fujian Provincial Natural Science Foundation[2021J01203] ; National Key Ramp;D Program of China[2022YFC3400500] ; National Key Ramp;D Program of China[2021ZD0203900] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[92253303] ; National Administration of Traditional Chinese Medicine[ZYYCXTD-202004] ; Department of Science and Technology of Guangdong Province ; High-level new Ramp;D institute[2019B090904008] ; High-level Innovative Research Institute[2021B0909050003] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| WOS记录号 | WOS:001030336400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306731]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Lin, Jin; Li, Jiacheng; Lin, Hua |
| 作者单位 | 1.Fujian Normal Univ, Coll Life Sci, Biomed Res Ctr South China, Fuzhou 350117, Peoples R China 2.Fujian Med Univ, Sch Pharm, Fuzhou 350122, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China 6.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China 7.Fujian Normal Univ, Coll Life Sci, Natl & Local United Engn Res Ctr Ind Microbiol & F, Fuzhou 350117, Fujian, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Rongkun,Yang, Jie,Liu, Ting,et al. Discovery of HyT-Based Degraders of CDK9-Cyclin T1 Complex[J]. CHEMISTRY & BIODIVERSITY,2023:10. |
| APA | Lin, Rongkun.,Yang, Jie.,Liu, Ting.,Wang, Mingyu.,Ke, Chongrong.,...&Lin, Hua.(2023).Discovery of HyT-Based Degraders of CDK9-Cyclin T1 Complex.CHEMISTRY & BIODIVERSITY,10. |
| MLA | Lin, Rongkun,et al."Discovery of HyT-Based Degraders of CDK9-Cyclin T1 Complex".CHEMISTRY & BIODIVERSITY (2023):10. |
入库方式： OAI收割
来源：上海药物研究所
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