Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC
文献类型：期刊论文
| 作者 | Chen, Jiexuan7; Wu, Mingfei7; Mo, Jun7; Hong, Ju5,7; Wang, Wei7; Jin, Yuheng7; Mao, Xinfei7; Liao, Xueyan7; Li, Kailin7; Yu, Xiaoli7 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-01-04 |
| 页码 | 15 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.4c02438 |
| 英文摘要 | The tedious synthesis and limited throughput biological evaluation remain a great challenge for discovering new proteolysis targeting chimera (PROTAC). To rapidly identify potential PROTAC lead compounds, we report a platform named Auto-RapTAC. Based on the modular characteristic of the PROTAC molecule, a streamlined workflow that integrates lab automation with "click chemistry" joint building-block libraries was constructed. This facilitates the autonomous generation of a variety of PROTACs, each with distinct linkers and E3 ligase ligands, all stored in biocompatible solutions. The ready-for-screening (R4S) approach, when paired with fluorescence-based assays, enables the efficient assessment of the PROTAC degradation activity in a high-throughput manner. To further test the capability of the platform, we identify six new PROTACs that target CDK2, CDK12, and BCL6 within a mere 8-day time frame for each target. In all, this platform could find broad application not only in discovering new PROTACs but also in the rapid development of novel heterobifunctional modalities. |
| WOS关键词 | CHRONIC LYMPHOCYTIC-LEUKEMIA ; PROTEIN-DEGRADATION ; CHEMISTRY ; TECHNOLOGIES ; DISCOVERY |
| 资助项目 | Key Research and Development Program of Zhejiang Province[82173660] ; National Natural Science Foundation of China[2022C03155] ; National Natural Science Foundation of China[2023C03112] ; Zhejiang Provincial Key Research & Development Plan |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001389980100001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315537]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Dong, Xiaowu; Che, Jinxin |
| 作者单位 | 1.Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Key Lab Clin Canc Pharmacol & Toxicol Res Zhejiang, Sch Med, Hangzhou 310024, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Zhejiang Univ, Coll Comp Sci & Technol, Hangzhou 310058, Peoples R China 4.Hangzhou Med Coll, Ctr Safety Evaluat & Res, Sch Pharm, Hangzhou 310013, Peoples R China 5.Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China 6.Zhejiang Univ, Hangzhou Inst Innovat Med, Hangzhou 310058, Peoples R China 7.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Jiexuan,Wu, Mingfei,Mo, Jun,et al. Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC[J]. JOURNAL OF MEDICINAL CHEMISTRY,2025:15. |
| APA | Chen, Jiexuan.,Wu, Mingfei.,Mo, Jun.,Hong, Ju.,Wang, Wei.,...&Che, Jinxin.(2025).Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC.JOURNAL OF MEDICINAL CHEMISTRY,15. |
| MLA | Chen, Jiexuan,et al."Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC".JOURNAL OF MEDICINAL CHEMISTRY (2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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