• 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

兰瑞肽和帕西瑞肽与生长抑素受体1结合模式的结构见解。

Structural insights into the binding modes of lanreotide and pasireotide with somatostatin receptor 1.

作者信息

Zeng Zicheng, Liao Qiwen, Gan Shiyi, Li Xinyu, Xiong Tiantian, Xu Lezhi, Li Dan, Jiang Yunlu, Chen Jing, Ye Richard, Du Yang, Wong Thiansze

机构信息

Kobilka Institute of Innovative Drug Discovery, School of Medicine, the Chinese University of Hong Kong, Shenzhen 518172, China.

Neurobiology Key Laboratory of Jining Medical University, Jining 272067, China.

出版信息

Acta Pharm Sin B. 2025 May;15(5):2468-2479. doi: 10.1016/j.apsb.2025.03.043. Epub 2025 Mar 20.

DOI:10.1016/j.apsb.2025.03.043
PMID:40487642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145065/
Abstract

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

摘要

生长抑素受体1（SSTR1）是治疗多种神经内分泌和肿瘤疾病的关键靶点。目前针对SSTR1的治疗方法，包括第一代生长抑素类似物兰瑞肽（Lan）和第二代类似物帕西瑞肽（Pas），虽展现出前景，但在选择性和疗效方面面临挑战。本研究展示了与Lan或Pas复合的SSTR1的高分辨率冷冻电镜结构，揭示了配体结合和激活的不同机制。这些结构阐明了每种配体诱导的SSTR1正构口袋中独特的构象变化，这对受体激活和配体选择性至关重要。结合生化分析和分子动力学模拟，我们的结果对SSTR家族内的结合特性进行了比较分析，突出了Lan和Pas激活SSTR1的细微差异。这些见解为通过提高受体亚型选择性来设计疗效增强、副作用减少的下一代疗法铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/106fa313089d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/a87a15c15504/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/ce8d5ddfdb24/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/b79480a3f3a2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/b8a93e0b3395/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/bf49dc580fba/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/525bd45bb7fd/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/106fa313089d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/a87a15c15504/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/ce8d5ddfdb24/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/b79480a3f3a2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/b8a93e0b3395/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/bf49dc580fba/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/525bd45bb7fd/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/12145065/106fa313089d/gr6.jpg

相似文献

1
Structural insights into the binding modes of lanreotide and pasireotide with somatostatin receptor 1.兰瑞肽和帕西瑞肽与生长抑素受体1结合模式的结构见解。
Acta Pharm Sin B. 2025 May;15(5):2468-2479. doi: 10.1016/j.apsb.2025.03.043. Epub 2025 Mar 20.
2
Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3.选择性配体识别和激活生长抑素受体 SSTR1 和 SSTR3。
Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2400298121. doi: 10.1073/pnas.2400298121. Epub 2024 Oct 3.
3
Structural insights into somatostatin receptor 5 bound with cyclic peptides.与环状肽结合的生长抑素受体 5 的结构见解。
Acta Pharmacol Sin. 2024 Nov;45(11):2432-2440. doi: 10.1038/s41401-024-01314-8. Epub 2024 Jun 26.
4
Pasireotide in the treatment of neuroendocrine tumors: a review of the literature.培高利特治疗神经内分泌肿瘤：文献复习。
Endocr Relat Cancer. 2018 Jun;25(6):R351-R364. doi: 10.1530/ERC-18-0010. Epub 2018 Apr 11.
5
Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues.环型生长抑素类似物激活生长抑素受体2的结构见解
Cell Discov. 2022 May 20;8(1):47. doi: 10.1038/s41421-022-00405-2.
6
Current role of pasireotide in the treatment of acromegaly.培高利特在肢端肥大症治疗中的当前作用。
Best Pract Res Clin Endocrinol Metab. 2024 Jul;38(4):101875. doi: 10.1016/j.beem.2024.101875. Epub 2024 Jan 24.
7
Molecular-Level Understanding of the Somatostatin Receptor 1 (SSTR1)-Ligand Binding: A Structural Biology Study Based on Computational Methods.生长抑素受体1（SSTR1）-配体结合的分子水平理解：基于计算方法的结构生物学研究
ACS Omega. 2020 Aug 11;5(33):21145-21161. doi: 10.1021/acsomega.0c02847. eCollection 2020 Aug 25.
8
Structural basis for the binding specificity of a SSTR1-selective analog of somatostatin.生长抑素SSTR1选择性类似物结合特异性的结构基础
Biochem Biophys Res Commun. 1999 May 19;258(3):689-94. doi: 10.1006/bbrc.1999.0699.
9
Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors.帕西瑞肽长效可重复制剂用于转移性神经内分泌肿瘤患者的II期临床试验。
Endocr Relat Cancer. 2015 Feb;22(1):1-9. doi: 10.1530/ERC-14-0360. Epub 2014 Nov 6.
10
Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data.帕西瑞肽治疗肢端肥大症：当前机制与临床数据概述
Neuroendocrinology. 2015;102(1-2):8-17. doi: 10.1159/000381460. Epub 2015 Mar 16.

本文引用的文献

1
Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues.环型生长抑素类似物激活生长抑素受体2的结构见解
Cell Discov. 2022 May 20;8(1):47. doi: 10.1038/s41421-022-00405-2.
2
Plasticity in ligand recognition at somatostatin receptors.生长抑素受体配体识别的可塑性。
Nat Struct Mol Biol. 2022 Mar;29(3):210-217. doi: 10.1038/s41594-022-00727-5. Epub 2022 Feb 24.
3
gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS.gmx_MMPBSA：一种使用GROMACS进行终态自由能计算的新工具。
J Chem Theory Comput. 2021 Oct 12;17(10):6281-6291. doi: 10.1021/acs.jctc.1c00645. Epub 2021 Sep 29.
4
Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report - a review.正常和肢端肥大症生长激素细胞中的生长抑素受体：临床医生对免疫组织化学报告的看法的转变——综述。
Rom J Morphol Embryol. 2020 Apr-Jun;61(2):353-359. doi: 10.47162/RJME.61.2.05.
5
International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.国际基础和临床药理学联合会。生长抑素受体：结构、功能、配体和新命名。
Pharmacol Rev. 2018 Oct;70(4):763-835. doi: 10.1124/pr.117.015388.
6
Pasireotide in the treatment of neuroendocrine tumors: a review of the literature.培高利特治疗神经内分泌肿瘤：文献复习。
Endocr Relat Cancer. 2018 Jun;25(6):R351-R364. doi: 10.1530/ERC-18-0010. Epub 2018 Apr 11.
7
Somatostatin receptor subtype 1 as a potential diagnostic marker and therapeutic target in prostate cancer.生长抑素受体亚型1作为前列腺癌潜在的诊断标志物和治疗靶点。
Prostate. 2017 Nov;77(15):1499-1511. doi: 10.1002/pros.23426. Epub 2017 Sep 14.
8
Management of the hormonal syndrome of neuroendocrine tumors.神经内分泌肿瘤激素综合征的管理
Arch Med Sci. 2017 Apr 1;13(3):515-524. doi: 10.5114/aoms.2016.60311. Epub 2016 Jun 1.
9
Dynamic monitoring of G-protein-mediated decreases of intracellular cAMP by FRET-based Epac sensors.利用基于荧光共振能量转移（FRET）的Epac传感器对G蛋白介导的细胞内cAMP减少进行动态监测。
Pflugers Arch. 2017 Jun;469(5-6):725-737. doi: 10.1007/s00424-017-1975-1. Epub 2017 Apr 6.
10
The Somatotrope Growth Hormone-Releasing Hormone/Growth Hormone/Insulin-Like Growth Factor-1 Axis in Immunoregulation and Immunosenescence.生长激素释放激素/生长激素/胰岛素样生长因子-1轴在免疫调节和免疫衰老中的作用
Front Horm Res. 2017;48:147-159. doi: 10.1159/000452913. Epub 2017 Feb 28.