An overview of PROTACs targeting KRAS and SOS1 as antitumor agents
文献类型：期刊论文
| 作者 | Han, Zhiqiu1,2,3; Wu, Qianping1,2,3; Rao, Hongxin1,2,3; Xu, Tianfeng1,2,3; Zhou, Chuan2 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2025-09-01 |
| 卷号 | 125页码:13 |
| 关键词 | KRAS SOS1 PROTAC Antitumor agent |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2025.130283 |
| 通讯作者 | Xu, Tianfeng(tfxu@simm.ac.cn) ; Zhou, Chuan(zhouchuan@simm.ac.cn) |
| 英文摘要 | KRAS is the most frequently mutated oncogene and its mutational activation drives approximately 25 % of human cancers. Son of Sevenless 1 (SOS1) plays a pivotal role in the KRAS signaling pathway through catalyzing the conversion of inactive GDP-bound KRAS to active GTP-bound KRAS, and is thus considered as a promising target for pan-KRAS inhibition. Currently, four KRASG12C-specific inhibitors, namely sotorasib, adagrasib, fulzerasib and garsorasib, have garnered regulatory approval. However, acquired resistance to KRASG12C inhibition rapidly emerges. In addition, the other prevalent KRAS mutations, including G12D and G12V, are still lacking effective therapeutic drugs. PROTAC-mediated KRAS and SOS1 degradation has been emerged as a promising strategy to overcome these issues, and achieved rapid progress in the recent years. This article provides an overview of the chemical structures, design strategies, structure-activity relationship (SAR) studies as well as in vitro and in vivo activities of the PROTACs degrading KRAS and SOS1, and sheds light on future challenges and opportunities to accelerate the development of new chemotherapies for KRAS-driven cancers. |
| WOS关键词 | INDUCED PROTEIN-DEGRADATION ; AMG 510 ; DISCOVERY ; RAS ; CANCER ; INHIBITOR |
| 资助项目 | Natural Science Foundation of Shanghai[20ZR1468500] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001498390000001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318213]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Tianfeng; Zhou, Chuan |
| 作者单位 | 1.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Han, Zhiqiu,Wu, Qianping,Rao, Hongxin,et al. An overview of PROTACs targeting KRAS and SOS1 as antitumor agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2025,125:13. |
| APA | Han, Zhiqiu,Wu, Qianping,Rao, Hongxin,Xu, Tianfeng,&Zhou, Chuan.(2025).An overview of PROTACs targeting KRAS and SOS1 as antitumor agents.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,125,13. |
| MLA | Han, Zhiqiu,et al."An overview of PROTACs targeting KRAS and SOS1 as antitumor agents".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 125(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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