• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

发现一种用于治疗转移性胰腺癌的新型RSK2抑制剂。

Discovery of a novel RSK2 inhibitor for the treatment of metastatic pancreatic cancer.

作者信息

Chung Chi-Hsiu, Hsu Kai-Cheng, Huang Ming-Min, Tu Huang-Ju, Pan Shiow-Lin, Chao Min-Wu

机构信息

School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

出版信息

J Enzyme Inhib Med Chem. 2025 Dec;40(1):2538673. doi: 10.1080/14756366.2025.2538673. Epub 2025 Aug 5.

DOI:10.1080/14756366.2025.2538673
PMID:40762406
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12326382/
Abstract

Pancreatic cancer is among the most lethal malignancies, with a five-year survival rate of only 6%. For patients with metastatic disease, current treatments extend median survival by merely four months. This study addresses the urgent need for targeted therapies, as no specific drugs are currently available. Clinical analyses revealed significantly elevated RSK2 expression in pancreatic cancer tissues, associated with shorter survival. We aimed to identify a novel RSK2 inhibitor for metastatic pancreatic cancer. Through structure-based virtual screening, we identified NSYSU-115 as a promising candidate with an IC50 of 45.5 nM. At low concentrations, NSYSU-115 significantly suppressed colony formation, while higher concentrations reduced cell viability and proliferation. It also inhibited phosphorylation of IκBα, a known RSK2 substrate, in a dose- and time-dependent manner. Furthermore, NSYSU-115 impaired cell migration and altered epithelial-mesenchymal transition (EMT) markers. These findings highlight NSYSU-115 as a potent kinase inhibitor with promising therapeutic potential for pancreatic cancer treatment.

摘要

胰腺癌是最致命的恶性肿瘤之一，五年生存率仅为6%。对于转移性疾病患者，目前的治疗方法仅将中位生存期延长了四个月。由于目前尚无特效药物，本研究满足了对靶向治疗的迫切需求。临床分析显示，胰腺癌组织中RSK2表达显著升高，与生存期缩短相关。我们旨在为转移性胰腺癌鉴定一种新型RSK2抑制剂。通过基于结构的虚拟筛选，我们确定NSYSU-115是一个有前景的候选药物，其IC50为45.5 nM。在低浓度下，NSYSU-115显著抑制集落形成，而高浓度则降低细胞活力和增殖。它还以剂量和时间依赖性方式抑制已知的RSK2底物IκBα的磷酸化。此外，NSYSU-115损害细胞迁移并改变上皮-间质转化（EMT）标志物。这些发现突出了NSYSU-115作为一种有效的激酶抑制剂，在胰腺癌治疗中具有广阔的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/c99cb28b8415/IENZ_A_2538673_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/1c8a64a869f5/IENZ_A_2538673_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/8512e676bde4/IENZ_A_2538673_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/d241a31a040c/IENZ_A_2538673_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/d689387d0bf1/IENZ_A_2538673_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/006750db7647/IENZ_A_2538673_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/127d37de697e/IENZ_A_2538673_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/f6ea5c3ad504/IENZ_A_2538673_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/6ff6e703f57d/IENZ_A_2538673_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/c99cb28b8415/IENZ_A_2538673_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/1c8a64a869f5/IENZ_A_2538673_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/8512e676bde4/IENZ_A_2538673_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/d241a31a040c/IENZ_A_2538673_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/d689387d0bf1/IENZ_A_2538673_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/006750db7647/IENZ_A_2538673_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/127d37de697e/IENZ_A_2538673_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/f6ea5c3ad504/IENZ_A_2538673_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/6ff6e703f57d/IENZ_A_2538673_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f29/12326382/c99cb28b8415/IENZ_A_2538673_F0009_B.jpg

相似文献

1
Discovery of a novel RSK2 inhibitor for the treatment of metastatic pancreatic cancer.发现一种用于治疗转移性胰腺癌的新型RSK2抑制剂。
J Enzyme Inhib Med Chem. 2025 Dec;40(1):2538673. doi: 10.1080/14756366.2025.2538673. Epub 2025 Aug 5.
2
and Molecular Analysis of Oleanolic Acid and Cisplatin on Pancreatic Cancer (Panc-1 Cell Line).齐墩果酸和顺铂对胰腺癌（Panc-1细胞系）的作用及分子分析
Anticancer Agents Med Chem. 2025;25(13):934-953. doi: 10.2174/0118715206336591241112061246.
3
Amiloride synergizes with EGFR PROTACs and inhibitors to overcome therapeutic resistance in NSCLC.氨氯吡咪与表皮生长因子受体（EGFR）靶向蛋白降解嵌合体（PROTAC）及抑制剂协同作用，以克服非小细胞肺癌（NSCLC）的治疗耐药性。
Bioorg Chem. 2025 Aug;163:108641. doi: 10.1016/j.bioorg.2025.108641. Epub 2025 Jun 4.
4
Virtual Screening and Biological Evaluation of T22306 as a Potent Third-generation EGFR Inhibitor for NSCLC Treatment.T22306作为一种用于非小细胞肺癌治疗的强效第三代表皮生长因子受体抑制剂的虚拟筛选及生物学评价
Anticancer Agents Med Chem. 2025;25(15):1128-1141. doi: 10.2174/0118715206362954250203103859.
5
Gracillin induces mitochondria-mediated apoptosis on pancreatic ductal adenocarcinoma through disruption of redox homeostasis via inhibiting NRF2/HO-1 antioxidant axis.格拉西林通过抑制NRF2/HO-1抗氧化轴破坏氧化还原稳态，从而诱导胰腺导管腺癌发生线粒体介导的凋亡。
Bioorg Chem. 2025 May 29;163:108636. doi: 10.1016/j.bioorg.2025.108636.
6
Discovery of flavonoid-containing compound Lupalbigenin as anti-NSCLC cancer agents via suppression of EGFR and ERK1/2 pathway.通过抑制EGFR和ERK1/2信号通路发现含黄酮类化合物卢帕双黄酮作为抗非小细胞肺癌药物
Bioorg Chem. 2024 Dec;153:107808. doi: 10.1016/j.bioorg.2024.107808. Epub 2024 Sep 7.
7
Systemic treatments for metastatic cutaneous melanoma.转移性皮肤黑色素瘤的全身治疗
Cochrane Database Syst Rev. 2018 Feb 6;2(2):CD011123. doi: 10.1002/14651858.CD011123.pub2.
8
Targeting MAP kinase for inhibiting Leishmania promastigotes and amastigotes stages by L-alanine derived molecules and their anticancer potential against PANC-1 cancer cell lines.通过L-丙氨酸衍生分子靶向丝裂原活化蛋白激酶以抑制利什曼原虫前鞭毛体和无鞭毛体阶段及其对PANC-1癌细胞系的抗癌潜力。
Bioorg Med Chem. 2025 Oct 1;128:118276. doi: 10.1016/j.bmc.2025.118276. Epub 2025 Jun 7.
9
PLAGL2 as a prognostic biomarker and an EMT-promoting factor in PDAC.PLAGL2作为胰腺癌的一种预后生物标志物和上皮-间质转化促进因子。
Sci Rep. 2025 Jul 14;15(1):25425. doi: 10.1038/s41598-025-09591-x.
10
Pioneering first-in-class HDAC-ROCK inhibitors as potential multitarget anticancer agents.开创性的一流HDAC-ROCK抑制剂作为潜在的多靶点抗癌药物。
Future Med Chem. 2025 Feb;17(4):393-407. doi: 10.1080/17568919.2025.2459589. Epub 2025 Jan 30.

本文引用的文献

1
Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors.整合公共数据集以发现和验证实体瘤中与生存相关的基因
Innovation (Camb). 2024 Apr 9;5(3):100625. doi: 10.1016/j.xinn.2024.100625. eCollection 2024 May 6.
2
Therapeutic targeting of p90 ribosomal S6 kinase.p90核糖体S6激酶的治疗靶点
Front Cell Dev Biol. 2023 Dec 19;11:1297292. doi: 10.3389/fcell.2023.1297292. eCollection 2023.
3
NF-κB signaling in neoplastic transition from epithelial to mesenchymal phenotype.
NF-κB 信号通路在肿瘤上皮-间充质转化过程中的作用。
Cell Commun Signal. 2023 Oct 18;21(1):291. doi: 10.1186/s12964-023-01207-z.
4
Synthesis and anti-tumor activity evaluation of 1H-pyrrolo[2,3-b]pyridine-2-carboxamide derivatives with phenyl sulfonamide groups as potent RSK2 inhibitors.具有苯磺酰胺基团的 1H-吡咯并[2,3-b]吡啶-2-甲酰胺衍生物的合成及其作为强效 RSK2 抑制剂的抗肿瘤活性评价。
Chem Biol Drug Des. 2024 Jan;103(1):e14376. doi: 10.1111/cbdd.14376. Epub 2023 Oct 18.
5
Transcriptome-level discovery of survival-associated biomarkers and therapy targets in non-small-cell lung cancer.非小细胞肺癌中与生存相关的生物标志物和治疗靶点的转录组水平发现。
Br J Pharmacol. 2024 Feb;181(3):362-374. doi: 10.1111/bph.16257. Epub 2023 Nov 23.
6
Pancreatic cancer: Advances and challenges.胰腺癌：进展与挑战。
Cell. 2023 Apr 13;186(8):1729-1754. doi: 10.1016/j.cell.2023.02.014.
7
RSK1 and RSK2 serine/threonine kinases regulate different transcription programs in cancer.RSK1和RSK2丝氨酸/苏氨酸激酶在癌症中调控不同的转录程序。
Front Cell Dev Biol. 2023 Jan 4;10:1015665. doi: 10.3389/fcell.2022.1015665. eCollection 2022.
8
The roles of intratumour heterogeneity in the biology and treatment of pancreatic ductal adenocarcinoma.肿瘤内异质性在胰腺导管腺癌生物学和治疗中的作用。
Oncogene. 2022 Oct;41(42):4686-4695. doi: 10.1038/s41388-022-02448-x. Epub 2022 Sep 10.
9
GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA.GEPIA2021：将多种基于去卷积的分析整合到 GEPIA 中。
Nucleic Acids Res. 2021 Jul 2;49(W1):W242-W246. doi: 10.1093/nar/gkab418.
10
Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.胰腺癌的转录表型是由肿瘤进化过程中的基因组事件驱动的。
Nat Genet. 2020 Feb;52(2):231-240. doi: 10.1038/s41588-019-0566-9. Epub 2020 Jan 13.