芳基膦酸是 Cdc25a 和 Cdc25b 磷酸酶的有效且同工型选择性抑制剂。
Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases.
机构信息
Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
出版信息
Bioorg Med Chem. 2012 Jul 15;20(14):4371-6. doi: 10.1016/j.bmc.2012.05.040. Epub 2012 May 24.
Abstract
Arylstibonates structurally resemble phosphotyrosine side chains in proteins and here we addressed the ability of such compounds to act as inhibitors of a panel of mammalian tyrosine and dual-specificity phosphatases. Two arylstibonates both possessing a carboxylate side chain were identified as potent inhibitors of the protein tyrosine phosphatase PTP-ß. In addition, they inhibited the dual-specificity, cell cycle regulatory phosphatases Cdc25a and Cdc25b with sub-micromolar potency. However, the Cdc25c phosphatase was not affected demonstrating that arylstibonates may be viable leads from which to develop isoform specific Cdc25 inhibitors.
摘要
芳基膦酸盐在结构上类似于蛋白质中的磷酸酪氨酸侧链，在这里我们研究了这些化合物作为一组哺乳动物酪氨酸和双特异性磷酸酶抑制剂的能力。两种都具有羧酸盐侧链的芳基膦酸盐被鉴定为蛋白酪氨酸磷酸酶 PTP-ß 的有效抑制剂。此外，它们以亚微摩尔的效力抑制双特异性、细胞周期调节磷酸酶 Cdc25a 和 Cdc25b。然而，Cdc25c 磷酸酶不受影响，表明芳基膦酸盐可能是开发 Cdc25 同工型特异性抑制剂的可行先导化合物。
相似文献
1
Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases.芳基膦酸是 Cdc25a 和 Cdc25b 磷酸酶的有效且同工型选择性抑制剂。
Bioorg Med Chem. 2012 Jul 15;20(14):4371-6. doi: 10.1016/j.bmc.2012.05.040. Epub 2012 May 24.
2
Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.以酪氨酸和双特异性蛋白磷酸酶抑制剂为重点的四氢吡喃酮酸文库的合成及其对VHR和cdc25B抑制作用的评估。
J Med Chem. 2001 Sep 27;44(20):3216-22. doi: 10.1021/jm0100741.
3
Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25.双特异性蛋白磷酸酶Cdc25新型强效抑制剂家族的发现及生物学评价
J Med Chem. 2001 Nov 22;44(24):4042-9. doi: 10.1021/jm0102046.
4
Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors.确定一种针对细胞周期蛋白依赖性激酶25双特异性磷酸酶抑制剂的强效且选择性药效团。
Mol Pharmacol. 2002 Apr;61(4):720-8. doi: 10.1124/mol.61.4.720.
5
Discovery of potent and selective Cdc25 phosphatase inhibitors via rapid assembly and in situ screening of Quinonoid-focused libraries.通过快速组装和原位筛选醌类化合物库发现有效的和选择性的 Cdc25 磷酸酶抑制剂。
Bioorg Chem. 2021 Oct;115:105254. doi: 10.1016/j.bioorg.2021.105254. Epub 2021 Aug 9.
6
A novel cinnamic acid derivative that inhibits Cdc25 dual-specificity phosphatase activity.一种抑制Cdc25双特异性磷酸酶活性的新型肉桂酸衍生物。
Cancer Sci. 2005 Sep;96(9):614-9. doi: 10.1111/j.1349-7006.2005.00086.x.
7
Identification of highly potent and selective Cdc25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries.从基于点击化学的组合文库的小型化中鉴定出高效且选择性的 Cdc25 蛋白磷酸酶抑制剂。
Eur J Med Chem. 2019 Dec 1;183:111696. doi: 10.1016/j.ejmech.2019.111696. Epub 2019 Sep 14.
8
Discovery of new inhibitors of Cdc25B dual specificity phosphatases by structure-based virtual screening.基于结构的虚拟筛选发现 Cdc25B 双特异性磷酸酶的新抑制剂。
J Med Chem. 2012 May 10;55(9):4142-58. doi: 10.1021/jm201624h. Epub 2012 May 1.
9
Cdc25B dual-specificity phosphatase inhibitors identified in a high-throughput screen of the NIH compound library.在国立卫生研究院化合物库的高通量筛选中鉴定出的Cdc25B双特异性磷酸酶抑制剂。
Assay Drug Dev Technol. 2009 Jun;7(3):250-65. doi: 10.1089/adt.2008.186.
10
Synthesis, anticancer activity, and molecular modeling of 1,4-naphthoquinones that inhibit MKK7 and Cdc25.1,4-萘醌类化合物的合成、抗癌活性及抑制 MKK7 和 Cdc25 的分子模拟。
Eur J Med Chem. 2019 Dec 1;183:111719. doi: 10.1016/j.ejmech.2019.111719. Epub 2019 Sep 18.
引用本文的文献
1
Cross-Species Complementation of Nonessential Yeast Genes Establishes Platforms for Testing Inhibitors of Human Proteins.跨物种非必需酵母基因互补建立了人类蛋白抑制剂测试平台。
Genetics. 2020 Mar;214(3):735-747. doi: 10.1534/genetics.119.302971. Epub 2020 Jan 14.
本文引用的文献
1
Characterisation of the PTEN inhibitor VO-OHpic.PTEN抑制剂VO-OHpic的特性分析
J Chem Biol. 2010 Oct;3(4):157-63. doi: 10.1007/s12154-010-0041-7. Epub 2010 Jun 4.
2
The therapeutic potential of phosphatase inhibitors.磷酸酶抑制剂的治疗潜力。
Curr Opin Chem Biol. 2009 Jun;13(3):272-83. doi: 10.1016/j.cbpa.2009.03.021. Epub 2009 May 4.
3
Arylstibonic acids: novel inhibitors and activators of human topoisomerase IB.芳基锑酸：人类拓扑异构酶IB的新型抑制剂和激活剂。
Bioorg Chem. 2008 Aug;36(4):190-7. doi: 10.1016/j.bioorg.2008.04.001. Epub 2008 May 27.
4
Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic acids.芳基次膦酸对人脱嘌呤/脱嘧啶内切核酸酶1的强效抑制作用。
Mol Pharmacol. 2008 Mar;73(3):669-77. doi: 10.1124/mol.107.042622. Epub 2007 Nov 27.
5
CDC25 phosphatases in cancer cells: key players? Good targets?癌细胞中的CDC25磷酸酶：关键角色？理想靶点？
Nat Rev Cancer. 2007 Jul;7(7):495-507. doi: 10.1038/nrc2169.
6
Cdc25 phosphatases: structure, specificity, and mechanism.细胞周期蛋白依赖性蛋白磷酸酶25：结构、特异性及作用机制
Biochemistry. 2007 Mar 27;46(12):3595-604. doi: 10.1021/bi700026j. Epub 2007 Mar 1.
7
A small molecule inhibitor for phosphatase and tensin homologue deleted on chromosome 10 (PTEN).一种针对10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）的小分子抑制剂。
ACS Chem Biol. 2006 Dec 15;1(12):780-90. doi: 10.1021/cb600352f.
8
The role of the C-terminal domain of protein tyrosine phosphatase-1B in phosphatase activity and substrate binding.蛋白酪氨酸磷酸酶-1B的C末端结构域在磷酸酶活性和底物结合中的作用。
J Biol Chem. 2007 Feb 2;282(5):2911-7. doi: 10.1074/jbc.M610096200. Epub 2006 Nov 29.
9
Protein tyrosine phosphatases: from genes, to function, to disease.蛋白质酪氨酸磷酸酶：从基因到功能再到疾病
Nat Rev Mol Cell Biol. 2006 Nov;7(11):833-46. doi: 10.1038/nrm2039.
10
Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells.一种线粒体磷酸酶参与胰腺β细胞中ATP生成和胰岛素分泌的调节。
Mol Cell. 2005 Jul 22;19(2):197-207. doi: 10.1016/j.molcel.2005.06.008.
Zotero 插件