Suppr超能文献

针对“不可成药”的癌症靶点研发药物。

Drugging the 'undruggable' cancer targets.

作者信息

Dang Chi V, Reddy E Premkumar, Shokat Kevan M, Soucek Laura

机构信息

Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Ludwig Institute for Cancer Research, New York, New York 10017, USA, and The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

出版信息

Nat Rev Cancer. 2017 Aug;17(8):502-508. doi: 10.1038/nrc.2017.36. Epub 2017 Jun 23.

Abstract

The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies. In this Viewpoint article, we asked four scientists working in this field for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.

摘要

“不可成药”一词是用来描述那些无法进行药理靶向作用的蛋白质。然而,针对其中许多靶点的“药物研发”正在取得进展,因此更合适的术语可能是“难以成药”或“尚未成药”。癌症中许多理想的靶点都属于这一类别,包括RAS和MYC致癌基因,对这些难以对付的蛋白质进行药理靶向现在是癌症研究中的一项关键挑战,这需要创新和新技术的开发。在这篇观点文章中,我们询问了四位在该领域工作的科学家,了解他们对最关键进展、挑战以及这一重要研究领域的未来前景的看法。

相似文献

1
Drugging the 'undruggable' cancer targets.针对“不可成药”的癌症靶点研发药物。
Nat Rev Cancer. 2017 Aug;17(8):502-508. doi: 10.1038/nrc.2017.36. Epub 2017 Jun 23.
2
Taking Aim at the Undruggable.直击不可成药靶点。
Am Soc Clin Oncol Educ Book. 2021 Mar;41:1-8. doi: 10.1200/EDBK_325885.
3
Strategies for targeting undruggable targets.靶向不可成药靶点的策略。
Expert Opin Drug Discov. 2022 Jan;17(1):55-69. doi: 10.1080/17460441.2021.1969359. Epub 2021 Aug 30.
5
Recent advances in cancer drug discovery targeting RAS.靶向RAS的癌症药物研发的最新进展
Drug Discov Today. 2016 Dec;21(12):1915-1919. doi: 10.1016/j.drudis.2016.08.002. Epub 2016 Aug 6.
6
Drugging Undruggable Molecular Cancer Targets.药物研发中的不可成药靶点
Annu Rev Pharmacol Toxicol. 2016;56:23-40. doi: 10.1146/annurev-pharmtox-010715-103440. Epub 2015 Nov 2.
8
Drugging RAS: Know the enemy.下药 RAS:知己知彼。
Science. 2017 Mar 17;355(6330):1158-1163. doi: 10.1126/science.aam7622. Epub 2017 Mar 16.

引用本文的文献

2
Druglike Molecular Degraders of the Oncogenic RNA-Binding Protein HuR.致癌性RNA结合蛋白HuR的类药物分子降解剂
JACS Au. 2025 Jul 16;5(8):3879-3891. doi: 10.1021/jacsau.5c00551. eCollection 2025 Aug 25.
4
DNA G-Quadruplexes as Targets for Natural Product Drug Discovery.作为天然产物药物发现靶点的DNA G-四链体
Engineering (Beijing). 2024 Jul;38:39-51. doi: 10.1016/j.eng.2024.03.015. Epub 2024 May 6.
6
RNA activation of improves leukemia treatment.RNA激活可改善白血病治疗。
Mol Ther Nucleic Acids. 2025 Jun 16;36(3):102611. doi: 10.1016/j.omtn.2025.102611. eCollection 2025 Sep 9.

本文引用的文献

1
Strategies to Inhibit Myc and Their Clinical Applicability.抑制Myc的策略及其临床应用
Front Cell Dev Biol. 2017 Feb 23;5:10. doi: 10.3389/fcell.2017.00010. eCollection 2017.
3
Multivalent Small-Molecule Pan-RAS Inhibitors.多价小分子泛RAS抑制剂
Cell. 2017 Feb 23;168(5):878-889.e29. doi: 10.1016/j.cell.2017.02.006.
4
Targeted protein degradation by PROTACs.通过 PROTACs 进行靶向蛋白降解。
Pharmacol Ther. 2017 Jun;174:138-144. doi: 10.1016/j.pharmthera.2017.02.027. Epub 2017 Feb 14.
5
How to unleash mitochondrial apoptotic blockades to kill cancers?如何解除线粒体凋亡阻滞以杀死癌细胞?
Acta Pharm Sin B. 2017 Jan;7(1):18-26. doi: 10.1016/j.apsb.2016.08.005. Epub 2016 Sep 21.
6
Induced protein degradation: an emerging drug discovery paradigm.诱导蛋白降解:一种新兴的药物发现模式。
Nat Rev Drug Discov. 2017 Feb;16(2):101-114. doi: 10.1038/nrd.2016.211. Epub 2016 Nov 25.
9
MYC, Metabolic Synthetic Lethality, and Cancer.MYC、代谢性合成致死与癌症
Recent Results Cancer Res. 2016;207:73-91. doi: 10.1007/978-3-319-42118-6_4.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验