• 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

相似文献

1
On-column ligand exchange for structure-based drug design: a case study with human 11β-hydroxysteroid dehydrogenase type 1.基于结构的药物设计中的柱上配体交换：以人11β-羟基类固醇脱氢酶1型为例的研究
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 May 1;68(Pt 5):601-5. doi: 10.1107/S1744309112010172. Epub 2012 Apr 21.
2
Discovery of novel inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 by docking and pharmacophore modeling.通过对接和药效团模型发现新型11β-羟基类固醇脱氢酶1型抑制剂
Bioorg Med Chem Lett. 2008 Feb 15;18(4):1340-5. doi: 10.1016/j.bmcl.2008.01.020. Epub 2008 Jan 11.
3
Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery.11β-羟甾脱氢酶 1 的晶体结构及其在药物发现中的应用。
Future Med Chem. 2011 Mar;3(3):367-90. doi: 10.4155/fmc.10.282.
4
Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1).11β-羟基类固醇脱氢酶1型（11β-HSD1）的芳基磺酰基哌嗪抑制剂的发现及初步构效关系研究
Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. doi: 10.1016/j.bmcl.2008.05.025. Epub 2008 May 10.
5
2-amino-1,3-thiazol-4(5H)-ones as potent and selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: enzyme-ligand co-crystal structure and demonstration of pharmacodynamic effects in C57Bl/6 mice.2-氨基-1,3-噻唑-4(5H)-酮作为强效和选择性11β-羟基类固醇脱氢酶1型抑制剂：酶-配体共晶体结构及在C57Bl/6小鼠中的药效学效应证明
J Med Chem. 2008 May 22;51(10):2933-43. doi: 10.1021/jm701551j. Epub 2008 Apr 18.
6
The discovery of new 11beta-hydroxysteroid dehydrogenase type 1 inhibitors by common feature pharmacophore modeling and virtual screening.通过共同特征药效团建模和虚拟筛选发现新型11β-羟基类固醇脱氢酶1型抑制剂
J Med Chem. 2006 Jun 15;49(12):3454-66. doi: 10.1021/jm0600794.
7
Identification of novel 11β-HSD1 inhibitors by combined ligand- and structure-based virtual screening.通过基于配体和结构的虚拟筛选联合鉴定新型11β-羟基类固醇脱氢酶1抑制剂
Mol Cell Endocrinol. 2014 Mar 25;384(1-2):71-82. doi: 10.1016/j.mce.2014.01.011. Epub 2014 Jan 18.
8
Synthesis and structure-activity relationship of 2-adamantylmethyl tetrazoles as potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).2-金刚烷基甲基四唑类化合物的合成及构效关系研究作为人 11β-羟甾脱氢酶 1 型（11β-HSD1）的有效和选择性抑制剂。
Bioorg Med Chem Lett. 2014 Jan 15;24(2):654-60. doi: 10.1016/j.bmcl.2013.11.066. Epub 2013 Dec 5.
9
Structure based design of 11β-HSD1 inhibitors.基于结构的 11β-HSD1 抑制剂设计。
Curr Pharm Biotechnol. 2010 Nov;11(7):779-91. doi: 10.2174/138920110792927748.
10
Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model.在体外酶抑制模型中发现具有口服活性的新型强效11β-羟基类固醇脱氢酶1型（11β-HSD1）苯甲酰胺抑制剂。
J Med Chem. 2008 Jul 10;51(13):3953-60. doi: 10.1021/jm800310g. Epub 2008 Jun 14.

本文引用的文献

1
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
REFMAC5 for the refinement of macromolecular crystal structures.用于大分子晶体结构精修的REFMAC5
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67. doi: 10.1107/S0907444911001314. Epub 2011 Mar 18.
3
Molecular replacement with MOLREP.使用MOLREP进行分子置换。
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5. doi: 10.1107/S0907444909042589. Epub 2009 Dec 21.
4
Efficacious 11beta-hydroxysteroid dehydrogenase type I inhibitors in the diet-induced obesity mouse model.饮食诱导肥胖小鼠模型中有效的11β-羟基类固醇脱氢酶1型抑制剂
J Med Chem. 2009 Sep 10;52(17):5449-61. doi: 10.1021/jm900639u.
5
Distinctive molecular inhibition mechanisms for selective inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1.人11β-羟基类固醇脱氢酶1型选择性抑制剂的独特分子抑制机制
Bioorg Med Chem. 2008 Oct 1;16(19):8922-31. doi: 10.1016/j.bmc.2008.08.065. Epub 2008 Aug 29.
6
Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model.在体外酶抑制模型中发现具有口服活性的新型强效11β-羟基类固醇脱氢酶1型（11β-HSD1）苯甲酰胺抑制剂。
J Med Chem. 2008 Jul 10;51(13):3953-60. doi: 10.1021/jm800310g. Epub 2008 Jun 14.
7
2-amino-1,3-thiazol-4(5H)-ones as potent and selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: enzyme-ligand co-crystal structure and demonstration of pharmacodynamic effects in C57Bl/6 mice.2-氨基-1,3-噻唑-4(5H)-酮作为强效和选择性11β-羟基类固醇脱氢酶1型抑制剂：酶-配体共晶体结构及在C57Bl/6小鼠中的药效学效应证明
J Med Chem. 2008 May 22;51(10):2933-43. doi: 10.1021/jm701551j. Epub 2008 Apr 18.
8
Structural characterization and pharmacodynamic effects of an orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor.一种口服活性11β-羟基类固醇脱氢酶1型抑制剂的结构表征及药效学效应
Chem Biol Drug Des. 2008 Jan;71(1):36-44. doi: 10.1111/j.1747-0285.2007.00603.x. Epub 2007 Dec 7.
9
Discovery and design of novel HSP90 inhibitors using multiple fragment-based design strategies.使用多种基于片段的设计策略发现和设计新型HSP90抑制剂。
Chem Biol Drug Des. 2007 Jul;70(1):1-12. doi: 10.1111/j.1747-0285.2007.00535.x.
10
Adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing's syndrome.肥胖症和库欣综合征中脂肪组织11β-羟类固醇脱氢酶1型的表达
Eur J Endocrinol. 2006 Sep;155(3):435-41. doi: 10.1530/eje.1.02228.

基于结构的药物设计中的柱上配体交换：以人11β-羟基类固醇脱氢酶1型为例的研究

On-column ligand exchange for structure-based drug design: a case study with human 11β-hydroxysteroid dehydrogenase type 1.

作者信息

Qin Wenying, Judge Russell A, Longenecker Kenton L, Solomon Larry R, Harlan John E

机构信息

Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.

出版信息

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 May 1;68(Pt 5):601-5. doi: 10.1107/S1744309112010172. Epub 2012 Apr 21.

DOI:10.1107/S1744309112010172
PMID:22691797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3374522/
Abstract

Successfully forming ligand-protein complexes with specific compounds can be a significant challenge in supporting structure-based drug design for a given protein target. In this respect, an on-column ligand- and detergent-exchange method was developed to obtain ligand-protein complexes of an adamantane series of compounds with 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) after a variety of other complexation methods had failed. This report describes the on-column exchange method and an unexpected byproduct of the method in which artificial trimers were observed in the structures.

摘要

对于给定的蛋白质靶点，成功地与特定化合物形成配体 - 蛋白质复合物可能是基于结构的药物设计面临的一项重大挑战。在这方面，在多种其他络合方法均失败后，开发了一种柱上配体和去污剂交换方法，以获得金刚烷系列化合物与11β - 羟基类固醇脱氢酶1型（11β - HSD1）的配体 - 蛋白质复合物。本报告描述了柱上交换方法以及该方法中一个意外的副产物，即在结构中观察到了人工三聚体。