用小分子转录因子模拟物抑制 ErbB2（Her2）表达。
Inhibition of ErbB2(Her2) expression with small molecule transcription factor mimics.
机构信息
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6233-6. doi: 10.1016/j.bmcl.2009.08.090. Epub 2009 Sep 1.
Abstract
Small molecules that mimic the transcriptional activation domain of eukaryotic transcriptional activators have the potential to serve as effective inhibitors of transcriptional processes. Here we show that one class of transcriptional activation domain mimics, amphipathic isoxazolidines, can be converted into inhibitors of gene expression mediated by the transcriptional activator ESX through small structural modifications. Addition of the small molecules leads to decreased expression of the cell surface growth receptor ErbB2(Her2) in ErbB2-positive cancer cells and, correspondingly, decreased proliferation.
摘要
小分子模拟真核转录激活因子的转录激活结构域，具有作为转录过程有效抑制剂的潜力。在这里，我们表明，一类转录激活结构域模拟物，两亲性异恶唑烷，可以通过小的结构修饰转化为转录激活因子 ESX 介导的基因表达抑制剂。小分子的添加导致 ErbB2 阳性癌细胞表面生长受体 ErbB2(Her2)表达降低，相应地，增殖减少。
相似文献
1
Inhibition of ErbB2(Her2) expression with small molecule transcription factor mimics.用小分子转录因子模拟物抑制 ErbB2（Her2）表达。
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6233-6. doi: 10.1016/j.bmcl.2009.08.090. Epub 2009 Sep 1.
2
Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth.ErbB2通过热休克因子1上调乳酸脱氢酶A促进乳腺癌细胞糖酵解和生长。
Oncogene. 2009 Oct 22;28(42):3689-701. doi: 10.1038/onc.2009.229. Epub 2009 Aug 10.
3
Genetic and chemical targeting of epithelial-restricted with serine box reduces EGF receptor and potentiates the efficacy of afatinib.上皮细胞限制性丝氨酸框的遗传和化学靶向减少表皮生长因子受体并增强阿法替尼的疗效。
Mol Cancer Ther. 2013 Aug;12(8):1515-25. doi: 10.1158/1535-7163.MCT-12-1110. Epub 2013 May 30.
4
A small molecule transcriptional activation domain.一个小分子转录激活结构域。
J Am Chem Soc. 2004 Sep 1;126(34):10504-5. doi: 10.1021/ja0473889.
5
ErbB2 activation of ESX gene expression.ErbB2对ESX基因表达的激活作用。
Oncogene. 2002 May 30;21(24):3934-8. doi: 10.1038/sj.onc.1205503.
6
HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer.HER2/ErbB2 激活 HSF1，从而控制 HSP90 客户，包括 HER2 过表达乳腺癌中的 MIF。
Cell Death Dis. 2014 Jan 2;5(1):e980. doi: 10.1038/cddis.2013.508.
7
Differential regulation of ErbB2 expression by cAMP-dependent protein kinase in tamoxifen-resistant breast cancer cells.环磷酸腺苷依赖性蛋白激酶对他莫昔芬耐药乳腺癌细胞中ErbB2表达的差异性调控
Arch Pharm Res. 2008 Mar;31(3):350-6. doi: 10.1007/s12272-001-1163-z. Epub 2008 Apr 13.
8
ERBB3 (HER3) is a key sensor in the regulation of ERBB-mediated signaling in both low and high ERBB2 (HER2) expressing cancer cells.ERBB3（HER3）是调节低表达和高表达 ERBB2（HER2）的癌细胞中 ERBB 介导信号转导的关键传感器。
Cancer Med. 2012 Aug;1(1):28-38. doi: 10.1002/cam4.10. Epub 2012 Jul 15.
9
Cell lineage tracing links ERα loss in Erbb2-positive breast cancers to the arising of a highly aggressive breast cancer subtype.细胞谱系追踪将 Erbb2 阳性乳腺癌中 ERα 的丢失与一种高度侵袭性乳腺癌亚型的出现联系起来。
Proc Natl Acad Sci U S A. 2021 May 25;118(21). doi: 10.1073/pnas.2100673118.
10
LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progression.LMO4是ErbB2/HER2/Neu诱导的乳腺癌细胞周期进程的重要介导因子。
Oncogene. 2009 Oct 15;28(41):3608-18. doi: 10.1038/onc.2009.221. Epub 2009 Aug 3.
引用本文的文献
1
Interrupting specific hydrogen bonds between ELF3 and MED23 as an alternative drug resistance-free strategy for HER2-overexpressing cancers.针对 HER2 过表达型癌症，打破 ELF3 和 MED23 间的特定氢键有望成为一种无耐药性的可选药物治疗策略。
J Adv Res. 2023 May;47:173-187. doi: 10.1016/j.jare.2022.08.003. Epub 2022 Aug 10.
2
Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides.新型异噁唑烷和同核苷γ-内酰胺类似物。
Molecules. 2019 Nov 6;24(22):4014. doi: 10.3390/molecules24224014.
3
Genetic and chemical targeting of epithelial-restricted with serine box reduces EGF receptor and potentiates the efficacy of afatinib.上皮细胞限制性丝氨酸框的遗传和化学靶向减少表皮生长因子受体并增强阿法替尼的疗效。
Mol Cancer Ther. 2013 Aug;12(8):1515-25. doi: 10.1158/1535-7163.MCT-12-1110. Epub 2013 May 30.
4
Stereoselective isoxazolidine synthesis via copper-catalyzed alkene aminooxygenation.铜催化烯烃氮氧环化反应立体选择性合成异噁唑烷。
J Org Chem. 2012 Sep 7;77(17):7755-60. doi: 10.1021/jo3013226. Epub 2012 Aug 15.
5
Synergistic enhancement of the potency and selectivity of small molecule transcriptional inhibitors.小分子转录抑制剂效力和选择性的协同增强。
ACS Med Chem Lett. 2012 Jan 12;3(1):30-34. doi: 10.1021/ml200186r.
6
Transcriptional tools: Small molecules for modulating CBP KIX-dependent transcriptional activators.转录工具：调节 CBP KIX 依赖性转录激活剂的小分子。
Biopolymers. 2011 Jan;95(1):17-23. doi: 10.1002/bip.21548.
7
Transcriptional switches: chemical approaches to gene regulation.转录开关：化学方法调控基因表达。
J Biol Chem. 2010 Apr 9;285(15):11033-8. doi: 10.1074/jbc.R109.075044. Epub 2010 Feb 10.
本文引用的文献
1
Direct inhibition of hypoxia-inducible transcription factor complex with designed dimeric epidithiodiketopiperazine.用设计的二聚体表二硫二肽抑制缺氧诱导因子复合物。
J Am Chem Soc. 2009 Dec 23;131(50):18078-88. doi: 10.1021/ja807601b.
2
Alternative inhibition of androgen receptor signaling: peptidomimetic pyrimidines as direct androgen receptor/coactivator disruptors.雄激素受体信号传导的替代抑制：拟肽嘧啶作为直接的雄激素受体/共激活因子破坏剂
ACS Chem Biol. 2009 Jun 19;4(6):435-40. doi: 10.1021/cb900043e.
3
Amphipathic small molecules mimic the binding mode and function of endogenous transcription factors.两亲性小分子模拟内源性转录因子的结合模式和功能。
ACS Chem Biol. 2009 May 15;4(5):335-44. doi: 10.1021/cb900028j.
4
Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site.在抗原结合位点与HER2和VEGF相互作用的抗体赫赛汀变体。
Science. 2009 Mar 20;323(5921):1610-4. doi: 10.1126/science.1165480.
5
Modification of HER2 pre-mRNA alternative splicing and its effects on breast cancer cells.HER2前体mRNA可变剪接的修饰及其对乳腺癌细胞的影响。
Int J Cancer. 2009 Feb 15;124(4):772-7. doi: 10.1002/ijc.24052.
6
The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines.拉帕替尼（一种表皮生长因子受体和人表皮生长因子受体2酪氨酸激酶的双重抑制剂）对胃癌细胞系的生长抑制作用。
Cancer Lett. 2008 Dec 18;272(2):296-306. doi: 10.1016/j.canlet.2008.07.018. Epub 2008 Sep 6.
7
Expanding the repertoire of small molecule transcriptional activation domains.拓展小分子转录激活域的种类
Bioorg Med Chem. 2009 Feb 1;17(3):1034-43. doi: 10.1016/j.bmc.2008.02.045. Epub 2008 Feb 16.
8
Generation of a set of simple, interpretable ADMET rules of thumb.生成一组简单、可解释的ADMET经验法则。
J Med Chem. 2008 Feb 28;51(4):817-34. doi: 10.1021/jm701122q. Epub 2008 Jan 31.
9
Transcriptional up-regulation in cells mediated by a small molecule.由小分子介导的细胞转录上调。
J Am Chem Soc. 2007 Sep 5;129(35):10654-5. doi: 10.1021/ja0736865. Epub 2007 Aug 11.
10
Helix mimetics as inhibitors of the interaction of the estrogen receptor with coactivator peptides.作为雌激素受体与共激活肽相互作用抑制剂的螺旋模拟物
Angew Chem Int Ed Engl. 2007;46(24):4471-3. doi: 10.1002/anie.200700657.
Zotero 插件