Recent advances in targeted degradation in the RAS pathway
文献类型：期刊论文
| 作者 | Ge, Zhiming5,6,7; Fan, Zisheng1,2,3,5; He, Wei4,5; Zhou, Guizhen1,2,3,5; Zhou, Yidi5,6,7; Zheng, Mingyue1,2,4,5,6,7 ; Zhang, Sulin5,6
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| 刊名 | FUTURE MEDICINAL CHEMISTRY
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| 出版日期 | 2025-03-19 |
| 卷号 | 17期号:6页码:693-708 |
| 关键词 | RAS cancer mutation degrader PROTAC |
| ISSN号 | 1756-8919 |
| DOI | 10.1080/17568919.2025.2476387 |
| 英文摘要 | RAS (rat sarcoma) is one of the most frequently mutated gene families in cancer, encoding proteins classified as small GTPases. Mutations in RAS proteins result in abnormal activation of the RAS signaling pathway, a key driver in the initiation and progression of various malignancies. Consequently, targeting RAS proteins and the RAS signaling pathway has become a critical strategy in anticancer therapy. While RAS was historically considered an "undruggable" target, recent breakthroughs have yielded inhibitors specifically targeting KRASG12C and KRASG12D mutations, which have shown clinical efficacy in patients. However, these inhibitors face limitations due to rapid acquired resistance and the toxic effects of combination therapies in clinical settings. Targeted protein degradation (TPD) strategies, such as PROTACs and molecular glues, provide a novel approach by selectively degrading RAS proteins, or their upstream and downstream regulatory factors, to block aberrant signaling pathways. These degraders offer a promising alternative to traditional inhibitors by potentially circumventing resistance and enhancing therapeutic precision. This review discusses recent advancements in RAS pathway degraders, with an emphasis on targeting RAS mutations as well as their upstream regulators and downstream effectors for potential cancer treatments. |
| WOS关键词 | K-RAS ; ACQUIRED-RESISTANCE ; ANTITUMOR-ACTIVITY ; SIGNALING PATHWAY ; MUTANT CANCERS ; POTENT ; INHIBITION ; DISCOVERY ; DEGRADER ; ERK |
| 资助项目 | National Natural Science Foundation of China[T2225002] ; National Natural Science Foundation of China[82273855] ; National Key Research and Development Program of China[2023YFC2305904] ; National Key Research and Development Program of China[2022YFC3400504] ; Youth Innovation Promotion Association CAS[2023296] ; Natural Science Foundation of Shanghai[22ZR1474300] ; Young Elite Scientists Sponsorship Program by CAST[2023QNRC001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001441894400001 |
| 出版者 | TAYLOR & FRANCIS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316554]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zheng, Mingyue; Zhang, Sulin |
| 作者单位 | 1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Lingang Lab, Shanghai, Peoples R China 4.Nanchang Univ, Sch Pharm, Nanchang, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ge, Zhiming,Fan, Zisheng,He, Wei,et al. Recent advances in targeted degradation in the RAS pathway[J]. FUTURE MEDICINAL CHEMISTRY,2025,17(6):693-708. |
| APA | Ge, Zhiming.,Fan, Zisheng.,He, Wei.,Zhou, Guizhen.,Zhou, Yidi.,...&Zhang, Sulin.(2025).Recent advances in targeted degradation in the RAS pathway.FUTURE MEDICINAL CHEMISTRY,17(6),693-708. |
| MLA | Ge, Zhiming,et al."Recent advances in targeted degradation in the RAS pathway".FUTURE MEDICINAL CHEMISTRY 17.6(2025):693-708. |
入库方式： OAI收割
来源：上海药物研究所
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