氨肽酶-N/CD13（EC 3.4.11.2）抑制剂：化学、生物学评价及治疗前景
Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects.
作者信息
Bauvois Brigitte, Dauzonne Daniel
机构信息
Unité INSERM 507, Hôpital Necker, Université René Descartes Paris V, Bâtiment Lavoisier, 161 rue de Sèvres, 75015 Paris, France.
出版信息
Med Res Rev. 2006 Jan;26(1):88-130. doi: 10.1002/med.20044.
Abstract
Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti-cancer and anti-inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.
摘要
氨肽酶N（APN）/CD13（EC 3.4.11.2）是一种跨膜蛋白酶，存在于多种人体组织和细胞类型（内皮细胞、上皮细胞、成纤维细胞、白细胞）中。APN/CD13的表达在炎症性疾病和癌症（实体瘤和血液肿瘤）中失调。APN/CD13作为冠状病毒的受体。APN活性的天然和合成抑制剂已得到表征。这些抑制剂表明，APN能够调节生物活性肽反应（疼痛管理、血管加压素释放），并影响免疫功能和主要生物学事件（细胞增殖、分泌、侵袭、血管生成）。因此，抑制APN/CD13可能会导致抗癌和抗炎药物的开发。本综述提供了已知天然和合成APN抑制剂的生物学和药理学概况的最新信息。就毒性和特异性而言，讨论了它们作为治疗剂的潜在用途的现状。
相似文献
1
Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects.氨肽酶-N/CD13（EC 3.4.11.2）抑制剂：化学、生物学评价及治疗前景
Med Res Rev. 2006 Jan;26(1):88-130. doi: 10.1002/med.20044.
2
Aminopeptidase N (CD13) as a target for cancer chemotherapy.氨肽酶 N（CD13）作为癌症化疗的靶点。
Cancer Sci. 2011 Mar;102(3):501-8. doi: 10.1111/j.1349-7006.2010.01826.x. Epub 2011 Jan 30.
3
The structure and main functions of aminopeptidase N.氨肽酶N的结构与主要功能。
Curr Med Chem. 2007;14(6):639-47. doi: 10.2174/092986707780059571.
4
Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin.抗血管生成剂姜黄素对CD13/氨肽酶N的不可逆抑制作用。
Chem Biol. 2003 Aug;10(8):695-704. doi: 10.1016/s1074-5521(03)00169-8.
5
Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry.新型亮氨酸脒基衍生物作为使用点击化学的氨基肽酶 N 抑制剂。
Bioorg Med Chem. 2018 Jul 23;26(12):3145-3157. doi: 10.1016/j.bmc.2018.04.041. Epub 2018 Apr 22.
6
Induction of the membrane alanyl aminopeptidase gene and surface expression in human T-cells by mitogenic activation.有丝分裂原激活诱导人T细胞中膜丙氨酰氨基肽酶基因的表达及表面表达。
Biochem J. 1996 Nov 1;319 ( Pt 3)(Pt 3):817-21. doi: 10.1042/bj3190817.
7
Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer.氨肽酶N（APN）/CD13抑制剂乌苯美司可增强人宫颈癌的放射敏感性。
BMC Cancer. 2008 Mar 19;8:74. doi: 10.1186/1471-2407-8-74.
8
Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II.亮氨酸脒基衍生物作为使用点击化学的氨基肽酶 N 抑制剂。第二部分。
Bioorg Med Chem. 2019 Mar 15;27(6):978-990. doi: 10.1016/j.bmc.2019.01.041. Epub 2019 Jan 31.
9
Design of Aminopeptidase N Inhibitors as Anti-cancer Agents.天冬氨酰蛋白酶 N 抑制剂的设计及其作为抗癌药物的应用。
J Med Chem. 2018 Aug 9;61(15):6468-6490. doi: 10.1021/acs.jmedchem.7b00782. Epub 2018 Apr 16.
10
Synthesis and 4D-QSAR Studies of Alanine Hydroxamic Acid Derivatives as Aminopeptidase N Inhibitors.丙氨酸羟肟酸衍生物作为氨肽酶 N 抑制剂的合成及 4D-QSAR 研究。
Med Chem. 2021;17(6):658-666. doi: 10.2174/1573406416666191227115451.
引用本文的文献
1
Aminopeptidase N: a multifunctional and promising target in medicinal chemistry.氨肽酶N：药物化学中一个多功能且有前景的靶点。
RSC Adv. 2025 Jul 23;15(32):26455-26472. doi: 10.1039/d5ra03038b. eCollection 2025 Jul 21.
2
Chemodiversity and Biotechnological Potential of Microginins.微精菌素的化学多样性与生物技术潜力
Int J Mol Sci. 2025 Jun 25;26(13):6117. doi: 10.3390/ijms26136117.
3
Imaging Heterogeneous Patterns of Aminopeptidase N Activity in Hierarchical Tissue Structures Through High-Resolution Whole-Organ 3D Mapping.通过高分辨率全器官三维映射成像分层组织结构中氨肽酶N活性的异质模式。
Angew Chem Int Ed Engl. 2025 May 26;64(22):e202504668. doi: 10.1002/anie.202504668. Epub 2025 Apr 14.
4
The DNA repair kinase ATM regulates CD13 expression and cell migration.DNA修复激酶ATM调节CD13的表达和细胞迁移。
Front Cell Dev Biol. 2024 Jun 12;12:1359105. doi: 10.3389/fcell.2024.1359105. eCollection 2024.
5
Biomarkers and Proteomics in Sarcomeric Hypertrophic Cardiomyopathy in the Young-FGF-21 Highly Associated with Overt Disease.年轻患者肌节性肥厚型心肌病中的生物标志物与蛋白质组学——FGF-21与显性疾病高度相关
J Cardiovasc Dev Dis. 2024 Mar 29;11(4):105. doi: 10.3390/jcdd11040105.
6
Distinguishing two distinct types of salivary extracellular vesicles: a potential tool for understanding their pathophysiological roles.区分两种不同类型的唾液细胞外囊泡：理解其病理生理作用的潜在工具。
Front Mol Biosci. 2024 Feb 28;11:1278955. doi: 10.3389/fmolb.2024.1278955. eCollection 2024.
7
Identification of activity-based biomarkers for early-stage pancreatic tumors in blood using single-molecule enzyme activity screening.利用单分子酶活性筛选技术在血液中鉴定早期胰腺癌的活性生物标志物。
Cell Rep Methods. 2024 Jan 22;4(1):100688. doi: 10.1016/j.crmeth.2023.100688. Epub 2024 Jan 12.
8
Bestatin, A Pluripotent Immunomodulatory Small Molecule, Drives Robust and Long-Lasting Immune Responses as an Adjuvant in Viral Vaccines.贝司他汀，一种多能免疫调节小分子，作为病毒疫苗的佐剂可激发强大且持久的免疫反应。
Vaccines (Basel). 2023 Nov 4;11(11):1690. doi: 10.3390/vaccines11111690.
9
Discovery of a Novel Ubenimex Derivative as a First-in-Class Dual CD13/Proteasome Inhibitor for the Treatment of Cancer.发现一种新型乌苯美司衍生物，作为一种首创的双重 CD13/蛋白酶体抑制剂，用于癌症治疗。
Molecules. 2023 Aug 30;28(17):6343. doi: 10.3390/molecules28176343.
10
A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis.成人和儿童急性髓系白血病细胞表达的免疫治疗靶点的直接比较和优先级排序：系统评价和荟萃分析。
Int J Mol Sci. 2023 Jun 2;24(11):9667. doi: 10.3390/ijms24119667.
本文引用的文献
1
N-hydroxy-2-(naphthalene-2-ylsulfanyl)-acetamide, a novel hydroxamic acid-based inhibitor of aminopeptidase N and its anti-angiogenic activity.N-羟基-2-（萘-2-基硫烷基）-乙酰胺，一种新型的基于异羟肟酸的氨肽酶N抑制剂及其抗血管生成活性。
Bioorg Med Chem Lett. 2005 Jan 3;15(1):181-3. doi: 10.1016/j.bmcl.2004.10.010.
2
Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice.氨肽酶抑制剂贝司他汀对原位接种于同基因小鼠的B16-BL6黑色素瘤细胞的抗肿瘤血管生成作用
Cancer Lett. 2004 Dec 8;216(1):35-42. doi: 10.1016/j.canlet.2004.06.050.
3
The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer.外肽酶CD10、CD13、CD26和CD143在胃癌中上调。
Int J Oncol. 2004 Nov;25(5):1223-32.
4
Compounds from Epilobium angustifolium inhibit the specific metallopeptidases ACE, NEP and APN.柳叶菜中的化合物可抑制特定的金属肽酶ACE、NEP和APN。
Planta Med. 2004 Oct;70(10):919-23. doi: 10.1055/s-2004-832617.
5
Human mitochondrial peptide deformylase, a new anticancer target of actinonin-based antibiotics.人线粒体肽脱甲酰基酶，一种基于放线诺宁的抗生素的新型抗癌靶点。
J Clin Invest. 2004 Oct;114(8):1107-16. doi: 10.1172/JCI22269.
6
Role of chemopreventive agents in cancer therapy.化学预防剂在癌症治疗中的作用。
Cancer Lett. 2004 Nov 25;215(2):129-40. doi: 10.1016/j.canlet.2004.07.013.
7
Cell signaling pathways altered by natural chemopreventive agents.天然化学预防剂改变的细胞信号通路。
Mutat Res. 2004 Nov 2;555(1-2):53-64. doi: 10.1016/j.mrfmmm.2004.04.015.
8
Cytotoxicity of psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication.来自两种海绵共生体的沙海葵毒素A的细胞毒性可能与DNA复制的抑制有关。
BMC Cancer. 2004 Sep 30;4:70. doi: 10.1186/1471-2407-4-70.
9
Identification of extra- and intracellular alanyl aminopeptidases as new targets to modulate keratinocyte growth and differentiation.鉴定细胞外和细胞内丙氨酰氨基肽酶作为调节角质形成细胞生长和分化的新靶点。
Biochem Biophys Res Commun. 2004 Sep 3;321(4):795-801. doi: 10.1016/j.bbrc.2004.07.029.
10
Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kappaB signaling.姜黄素通过调节核因子-κB信号通路抑制人头颈部鳞状细胞癌细胞的生长和存活。
Int J Cancer. 2004 Sep 20;111(5):679-92. doi: 10.1002/ijc.20333.
Zotero 插件