• 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
Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening.基于结构的虚拟筛选的吡唑骨架蛋白酶体抑制剂。
J Med Chem. 2015 Feb 26;58(4):2036-41. doi: 10.1021/jm501344n. Epub 2015 Feb 17.
2
Design and synthesis of tripeptidyl furylketones as selective inhibitors against the β5 subunit of human 20S proteasome.三肽基呋喃酮类化合物的设计与合成：作为选择性抑制人 20S 蛋白酶体β5 亚基的抑制剂。
Eur J Med Chem. 2020 Apr 15;192:112160. doi: 10.1016/j.ejmech.2020.112160. Epub 2020 Feb 19.
3
Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.发现新型三肽环氧丙烷蛋白酶体抑制剂用于治疗多发性骨髓瘤。
Bioorg Med Chem. 2021 Jun 15;40:116182. doi: 10.1016/j.bmc.2021.116182. Epub 2021 May 1.
4
Discovery of a novel dipeptidyl boronic acid proteasome inhibitor for the treatment of multiple myeloma and triple-negative breast cancer.新型二肽硼酸蛋白酶体抑制剂的发现及其在多发性骨髓瘤和三阴性乳腺癌治疗中的应用。
Org Biomol Chem. 2019 Jan 16;17(3):683-691. doi: 10.1039/c8ob02668h.
5
Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism studies.新型二肽硼酸蛋白酶体抑制剂的设计、合成、体外和体内评价及构效关系（SAR）探讨作为口服抗肿瘤药物用于治疗多发性骨髓瘤及作用机制研究。
Bioorg Med Chem. 2018 Aug 7;26(14):3975-3981. doi: 10.1016/j.bmc.2018.06.020. Epub 2018 Jun 18.
6
Blockade of the malignant phenotype by β-subunit selective noncovalent inhibition of immuno- and constitutive proteasomes.通过β亚基选择性非共价抑制免疫蛋白酶体和组成型蛋白酶体来阻断恶性表型
Oncotarget. 2017 Feb 7;8(6):10437-10449. doi: 10.18632/oncotarget.14428.
7
Identification of novel gankyrin binding scaffolds by high throughput virtual screening.通过高通量虚拟筛选鉴定新型甘菊环素结合支架
Bioorg Med Chem Lett. 2021 Jul 1;43:128043. doi: 10.1016/j.bmcl.2021.128043. Epub 2021 Apr 16.
8
Development of small molecule-drug conjugates based on derivatives of natural proteasome inhibitors that exhibit selectivity for PSMA-expressing cancer cells.基于天然蛋白酶体抑制剂衍生物的小分子药物偶联物的开发，这些衍生物对表达 PSMA 的癌细胞具有选择性。
Bioorg Med Chem. 2024 Jun 15;108:117773. doi: 10.1016/j.bmc.2024.117773. Epub 2024 Jun 3.
9
Cytotoxic unsaturated electrophilic compounds commonly target the ubiquitin proteasome system.细胞毒性不饱和亲电化合物通常靶向泛素蛋白酶体系统。
Sci Rep. 2019 Jul 8;9(1):9841. doi: 10.1038/s41598-019-46168-x.
10
Design, synthesis, and biological evaluation of novel phenol ether derivatives as non-covalent proteasome inhibitors.新型酚醚衍生物的设计、合成及作为非共价蛋白酶体抑制剂的生物评价。
Eur J Med Chem. 2019 Jan 1;161:543-558. doi: 10.1016/j.ejmech.2018.10.056. Epub 2018 Oct 26.

引用本文的文献

1
Primed for Interactions: Investigating the Primed Substrate Channel of the Proteasome for Improved Molecular Engagement.做好相互作用的准备：研究蛋白酶体的预激活底物通道以改善分子结合。
Molecules. 2024 Jul 17;29(14):3356. doi: 10.3390/molecules29143356.
2
A Shortcut from Genome to Drug: The Employment of Bioinformatic Tools to Find New Targets for Gastric Cancer Treatment.从基因组到药物的捷径：利用生物信息学工具寻找胃癌治疗新靶点
Pharmaceutics. 2023 Sep 12;15(9):2303. doi: 10.3390/pharmaceutics15092303.
3
Attempting to Increase the Effectiveness of the Antidepressant Trazodone Hydrochloride Drug Using π-Acceptors.尝试使用π-受体来提高抗抑郁药盐酸曲唑酮的疗效。
Int J Environ Res Public Health. 2022 Sep 8;19(18):11281. doi: 10.3390/ijerph191811281.
4
Developing New Treatments for COVID-19 through Dual-Action Antiviral/Anti-Inflammatory Small Molecules and Physiologically Based Pharmacokinetic Modeling.通过双作用抗病毒/抗炎小分子和基于生理的药代动力学模型开发 COVID-19 的新疗法。
Int J Mol Sci. 2022 Jul 20;23(14):8006. doi: 10.3390/ijms23148006.
5
Drug Discovery for Using Structure-Based Computer-Aided Drug Design Approach.基于结构的计算机辅助药物设计方法在药物发现中的应用。
Int J Mol Sci. 2021 Dec 9;22(24):13259. doi: 10.3390/ijms222413259.
6
Bioactive recombinant human oncostatin M for NMR-based screening in drug discovery.用于药物发现中基于 NMR 的筛选的生物活性重组人肿瘤坏死因子相关凋亡诱导配体。
Sci Rep. 2021 Aug 10;11(1):16174. doi: 10.1038/s41598-021-95424-6.
7
An Updated Review of Computer-Aided Drug Design and Its Application to COVID-19.计算机辅助药物设计及其在 COVID-19 中的应用的最新综述。
Biomed Res Int. 2021 Jun 24;2021:8853056. doi: 10.1155/2021/8853056. eCollection 2021.
8
Ubiquitination Regulators Discovered by Virtual Screening for the Treatment of Cancer.通过虚拟筛选发现用于癌症治疗的泛素化调节剂。
Front Cell Dev Biol. 2021 May 12;9:665646. doi: 10.3389/fcell.2021.665646. eCollection 2021.
9
Novel Compounds Identified by Structure-Based Prion Disease Drug Discovery Using In Silico Screening Delay the Progression of an Illness in Prion-Infected Mice.基于结构的朊病毒病药物发现的计算筛选鉴定的新型化合物可延缓感染朊病毒的小鼠疾病的进展。
Neurotherapeutics. 2020 Oct;17(4):1836-1849. doi: 10.1007/s13311-020-00903-9.
10
Assessing and improving the performance of consensus docking strategies using the DockBox package.使用 DockBox 包评估和改进共识对接策略的性能。
J Comput Aided Mol Des. 2019 Sep;33(9):817-829. doi: 10.1007/s10822-019-00227-7. Epub 2019 Oct 1.

本文引用的文献

1
Selective immunoproteasome inhibitors with non-peptide scaffolds identified from structure-based virtual screening.通过基于结构的虚拟筛选鉴定出的具有非肽骨架的选择性免疫蛋白酶体抑制剂。
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3614-7. doi: 10.1016/j.bmcl.2014.05.025. Epub 2014 May 17.
2
A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.卡非佐米 2-10 分钟输注治疗晚期实体瘤患者的 I/II 期研究。
Cancer Chemother Pharmacol. 2013 Oct;72(4):861-8. doi: 10.1007/s00280-013-2267-x. Epub 2013 Aug 25.
3
Inhibition of the human proteasome by imidazoline scaffolds.咪唑烷骨架对人蛋白酶体的抑制作用。
J Med Chem. 2013 Jul 25;56(14):5974-8. doi: 10.1021/jm400235r. Epub 2013 Jul 3.
4
U.s. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma.美国食品和药物管理局批准：卡非佐米治疗多发性骨髓瘤。
Clin Cancer Res. 2013 Sep 1;19(17):4559-63. doi: 10.1158/1078-0432.CCR-13-0755. Epub 2013 Jun 17.
5
Homopiperazine derivatives as a novel class of proteasome inhibitors with a unique mode of proteasome binding.作为一类新型的蛋白酶体抑制剂，同哌嗪衍生物具有独特的蛋白酶体结合模式。
PLoS One. 2013 Apr 11;8(4):e60649. doi: 10.1371/journal.pone.0060649. Print 2013.
6
From epoxomicin to carfilzomib: chemistry, biology, and medical outcomes.从 epoxy 霉素到卡非佐米：化学、生物学和医学结果。
Nat Prod Rep. 2013 May;30(5):600-4. doi: 10.1039/c3np20126k.
7
Potent proteasome inhibitors derived from the unnatural cis-cyclopropane isomer of Belactosin A: synthesis, biological activity, and mode of action.来源于非天然顺式环丙烷异构贝拉唑素 A 的强效蛋白酶体抑制剂：合成、生物活性和作用模式。
J Med Chem. 2013 May 9;56(9):3689-700. doi: 10.1021/jm4002296. Epub 2013 Apr 22.
8
Proteasome inhibitors in the treatment of multiple myeloma.蛋白酶体抑制剂在多发性骨髓瘤治疗中的应用。
Expert Rev Anticancer Ther. 2013 Mar;13(3):339-58. doi: 10.1586/era.13.9.
9
Noncompetitive modulation of the proteasome by imidazoline scaffolds overcomes bortezomib resistance and delays MM tumor growth in vivo.通过咪唑烷骨架对蛋白酶体的非竞争性调节克服硼替佐米耐药性并延缓体内 MM 肿瘤生长。
ACS Chem Biol. 2013 Mar 15;8(3):578-87. doi: 10.1021/cb300568r. Epub 2012 Dec 11.
10
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.卡非佐米的临床药代动力学、代谢和药物相互作用。
Drug Metab Dispos. 2013 Jan;41(1):230-7. doi: 10.1124/dmd.112.047662. Epub 2012 Nov 1.

基于结构的虚拟筛选的吡唑骨架蛋白酶体抑制剂。

Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.

出版信息

J Med Chem. 2015 Feb 26;58(4):2036-41. doi: 10.1021/jm501344n. Epub 2015 Feb 17.

DOI:10.1021/jm501344n
PMID:25658656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11790068/
Abstract

We performed a virtual screen of ∼340 000 small molecules against the active site of proteasomes followed by in vitro assays and subsequent optimization, yielding a proteasome inhibitor with pyrazole scaffold. The pyrazole-scaffold compound displayed excellent metabolic stability and was highly effective in suppressing solid tumor growth in vivo. Furthermore, the effectiveness of this compound was not negatively impacted by resistance to bortezomib or carfilzomib.

摘要

我们对蛋白酶体的活性位点进行了约 340000 种小分子的虚拟筛选，随后进行了体外检测和后续优化，得到了一种具有吡唑骨架的蛋白酶体抑制剂。该吡唑骨架化合物具有优异的代谢稳定性，并在体内有效地抑制了实体肿瘤的生长。此外，该化合物的有效性不受硼替佐米或卡非佐米耐药性的影响。