通过ANCHOR.QUERY进行骨架跳跃：β-内酰胺作为有效的p53-MDM2拮抗剂。
Scaffold hopping via ANCHOR.QUERY: β-lactams as potent p53-MDM2 antagonists.
作者信息
Shaabani S, Neochoritis C G, Twarda-Clapa A, Musielak B, Holak T A, Dömling A
机构信息
Department of Drug Design, University of Groningen, The Netherlands.
Faculty of Chemistry, Shahid Beheshti University, Tehran, Iran.
出版信息
Medchemcomm. 2017 May 1;8(5):1046-1052. doi: 10.1039/C7MD00058H. Epub 2017 Mar 15.
Abstract
Using the pharmacophore-based virtual screening platform ANCHOR.QUERY, we morphed our recently described Ugi-4CR scaffold towards a β-lactam scaffold with potent p53-MDM2 antagonizing activities. 2D-HSQC and FP measurements confirm potent MDM2 binding. Molecular modeling studies are used to understand the observed SAR in the β-lactam series.
摘要
使用基于药效团的虚拟筛选平台ANCHOR.QUERY，我们将最近描述的乌吉-4CR支架转变为具有有效p53-MDM2拮抗活性的β-内酰胺支架。二维异核单量子相干谱（2D-HSQC）和荧光偏振（FP）测量证实了其与MDM2的有效结合。分子建模研究用于理解β-内酰胺系列中观察到的构效关系（SAR）。
相似文献
1
Scaffold hopping via ANCHOR.QUERY: β-lactams as potent p53-MDM2 antagonists.通过ANCHOR.QUERY进行骨架跳跃：β-内酰胺作为有效的p53-MDM2拮抗剂。
Medchemcomm. 2017 May 1;8(5):1046-1052. doi: 10.1039/C7MD00058H. Epub 2017 Mar 15.
2
Rational design and synthesis of 1,5-disubstituted tetrazoles as potent inhibitors of the MDM2-p53 interaction.作为MDM2-p53相互作用强效抑制剂的1,5-二取代四唑的合理设计与合成
Eur J Med Chem. 2017 Jan 27;126:384-407. doi: 10.1016/j.ejmech.2016.11.029. Epub 2016 Nov 16.
3
Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction.在运动中打击：针对 MDM2-p53 相互作用的固有无序蛋白质状态。
Eur J Med Chem. 2019 Nov 15;182:111588. doi: 10.1016/j.ejmech.2019.111588. Epub 2019 Aug 6.
4
Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists.基于吲哚和多组分反应的大环化合物作为p53-MDM2拮抗剂的设计
Beilstein J Org Chem. 2019 Feb 20;15:513-520. doi: 10.3762/bjoc.15.45. eCollection 2019.
5
Artificial Macrocycles as Potent p53-MDM2 Inhibitors.作为强效p53-MDM2抑制剂的人工大环化合物
ACS Med Chem Lett. 2017 Sep 20;8(10):1025-1030. doi: 10.1021/acsmedchemlett.7b00219. eCollection 2017 Oct 12.
6
[Scaffold hopping computational approach for searching novel β-lactamase inhibitors].用于搜索新型β-内酰胺酶抑制剂的支架跳跃计算方法
Biomed Khim. 2019 Oct;65(6):468-476. doi: 10.18097/PBMC20196506468.
7
A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53 osteosarcoma cells.一种基于氟吲哚的 MDM2 拮抗剂，能选择性抑制 p53 成骨肉瘤细胞的生长。
FEBS J. 2019 Apr;286(7):1360-1374. doi: 10.1111/febs.14774. Epub 2019 Feb 16.
8
Identification of High Affinity Non-Peptidic Small Molecule Inhibitors of MDM2-p53 Interactions through Structure-Based Virtual Screening Strategies.通过基于结构的虚拟筛选策略鉴定MDM2-p53相互作用的高亲和力非肽小分子抑制剂。
Asian Pac J Cancer Prev. 2015;16(9):3759-65. doi: 10.7314/apjcp.2015.16.9.3759.
9
Optimization beyond AMG 232: discovery and SAR of sulfonamides on a piperidinone scaffold as potent inhibitors of the MDM2-p53 protein-protein interaction.超越AMG 232的优化：哌啶酮支架上磺酰胺类化合物作为MDM2-p53蛋白-蛋白相互作用强效抑制剂的发现与构效关系研究
Bioorg Med Chem Lett. 2014 Aug 15;24(16):3782-5. doi: 10.1016/j.bmcl.2014.06.073. Epub 2014 Jul 1.
10
Forging New Scaffolds from Old: Combining Scaffold Hopping and Hierarchical Virtual Screening for Identifying Novel Bcl-2 Inhibitors.从旧的支架中开拓新的领域：结合支架跳跃和层次虚拟筛选鉴定新型 Bcl-2 抑制剂。
Curr Top Med Chem. 2019;19(13):1162-1172. doi: 10.2174/1568026619666190618142432.
引用本文的文献
1
Query-guided protein-protein interaction inhibitor discovery.基于查询的蛋白质-蛋白质相互作用抑制剂发现
Chem Sci. 2021 Mar 2;12(13):4753-4762. doi: 10.1039/d1sc00023c.
2
The Groebke-Blackburn-Bienaymé Reaction.格罗布克-布莱克本-比内梅反应
Eur J Chem. 2019 Nov 14;2019(42):7007-7049. doi: 10.1002/ejoc.201901124. Epub 2019 Aug 30.
3
TEAD-YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics.DNA 编码吲哚聚焦的 Ugi 肽模拟物中的 TEAD-YAP 相互作用抑制剂和 MDM2 结合物。
Angew Chem Int Ed Engl. 2020 Nov 9;59(46):20338-20342. doi: 10.1002/anie.202006280. Epub 2020 Jul 15.
4
Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction.在运动中打击：针对 MDM2-p53 相互作用的固有无序蛋白质状态。
Eur J Med Chem. 2019 Nov 15;182:111588. doi: 10.1016/j.ejmech.2019.111588. Epub 2019 Aug 6.
5
Artificial Macrocycles.人工大环化合物
Synlett. 2018 Jun;29(9):1136-1151. doi: 10.1055/s-0036-1591975. Epub 2018 May 7.
6
Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists.基于吲哚和多组分反应的大环化合物作为p53-MDM2拮抗剂的设计
Beilstein J Org Chem. 2019 Feb 20;15:513-520. doi: 10.3762/bjoc.15.45. eCollection 2019.
7
A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53 osteosarcoma cells.一种基于氟吲哚的 MDM2 拮抗剂，能选择性抑制 p53 成骨肉瘤细胞的生长。
FEBS J. 2019 Apr;286(7):1360-1374. doi: 10.1111/febs.14774. Epub 2019 Feb 16.
8
Tetrazoles via Multicomponent Reactions.四唑类化合物的多组分反应合成法。
Chem Rev. 2019 Feb 13;119(3):1970-2042. doi: 10.1021/acs.chemrev.8b00564. Epub 2019 Feb 1.
9
Artificial Macrocycles as Potent p53-MDM2 Inhibitors.作为强效p53-MDM2抑制剂的人工大环化合物
ACS Med Chem Lett. 2017 Sep 20;8(10):1025-1030. doi: 10.1021/acsmedchemlett.7b00219. eCollection 2017 Oct 12.
10
AnchorQuery: Rapid online virtual screening for small-molecule protein-protein interaction inhibitors.锚定查询：用于小分子蛋白质-蛋白质相互作用抑制剂的快速在线虚拟筛选
Protein Sci. 2018 Jan;27(1):229-232. doi: 10.1002/pro.3303. Epub 2017 Oct 24.
本文引用的文献
1
Recent Advances in Scaffold Hopping.骨架跃迁的最新进展
J Med Chem. 2017 Feb 23;60(4):1238-1246. doi: 10.1021/acs.jmedchem.6b01437. Epub 2016 Dec 21.
2
Rational design and synthesis of 1,5-disubstituted tetrazoles as potent inhibitors of the MDM2-p53 interaction.作为MDM2-p53相互作用强效抑制剂的1,5-二取代四唑的合理设计与合成
Eur J Med Chem. 2017 Jan 27;126:384-407. doi: 10.1016/j.ejmech.2016.11.029. Epub 2016 Nov 16.
3
A Unique Mdm2-Binding Mode of the 3-Pyrrolin-2-one- and 2-Furanone-Based Antagonists of the p53-Mdm2 Interaction.基于3-吡咯啉-2-酮和2-呋喃酮的p53-Mdm2相互作用拮抗剂的独特Mdm2结合模式
ACS Chem Biol. 2016 Dec 16;11(12):3310-3318. doi: 10.1021/acschembio.6b00596. Epub 2016 Oct 17.
4
How To Design a Successful p53-MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures.如何设计一种成功的p53-MDM2/X相互作用抑制剂：基于晶体结构的全面概述
ChemMedChem. 2016 Apr 19;11(8):757-72. doi: 10.1002/cmdc.201500487. Epub 2015 Dec 16.
5
Multicomponent Reactions, Union of MCRs and Beyond.多组分反应，MCR 的联合及超越。
Chem Rec. 2015 Oct;15(5):981-96. doi: 10.1002/tcr.201500201. Epub 2015 Sep 11.
6
NMR-based approaches for the identification and optimization of inhibitors of protein-protein interactions.基于核磁共振的蛋白质-蛋白质相互作用抑制剂的鉴定与优化方法。
Chem Rev. 2014 May 14;114(9):4749-63. doi: 10.1021/cr500043b. Epub 2014 Apr 8.
7
The p53-MDM2/MDMX axis - A chemotype perspective.p53-MDM2/MDMX轴——从化学型角度看
Medchemcomm. 2011;2:246-260. doi: 10.1039/C0MD00248H.
8
Discovery of highly potent p53-MDM2 antagonists and structural basis for anti-acute myeloid leukemia activities.发现强效 p53-MDM2 拮抗剂及抗急性髓系白血病活性的结构基础。
ACS Chem Biol. 2014 Mar 21;9(3):802-11. doi: 10.1021/cb400728e. Epub 2014 Jan 17.
9
Hitting a moving target: targeting transient protein states.击中移动目标：靶向瞬时蛋白质状态。
Structure. 2013 Dec 3;21(12):2095-7. doi: 10.1016/j.str.2013.11.003.
10
Transient protein states in designing inhibitors of the MDM2-p53 interaction.设计 MDM2-p53 相互作用抑制剂中的瞬态蛋白态。
Structure. 2013 Dec 3;21(12):2143-51. doi: 10.1016/j.str.2013.09.006. Epub 2013 Oct 24.
Zotero 插件