{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:42:21Z","timestamp":1778276541192,"version":"3.51.4"},"reference-count":117,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>PDZ (postsynaptic density (PSD95), discs large (Dlg), and zonula occludens (ZO-1)-dependent interactions are widely distributed within different cell types and regulate a variety of cellular processes. To date, some of these interactions have been identified as targets of small molecules or peptides, mainly related to central nervous system disorders and cancer. Recently, the knowledge of PDZ proteins and their interactions has been extended to various cell types of the immune system, suggesting that their targeting by viral pathogens may constitute an immune evasion mechanism that favors viral replication and dissemination. Thus, the pharmacological modulation of these interactions, either with small molecules or peptides, could help in the control of some immune-related diseases. Deeper structural and functional knowledge of this kind of protein\u2013protein interactions, especially in immune cells, will uncover novel pharmacological targets for a diversity of clinical conditions.<\/jats:p>","DOI":"10.3390\/molecules26216367","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T23:27:39Z","timestamp":1634858859000},"page":"6367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Peptide Targeting of PDZ-Dependent Interactions as Pharmacological Intervention in Immune-Related Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-0448","authenticated-orcid":false,"given":"Luis H.","family":"Guti\u00e9rrez-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Virology and Mycology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-417X","authenticated-orcid":false,"given":"Selma","family":"Rivas-Fuentes","sequence":"additional","affiliation":[{"name":"Department of Research on Biochemistry, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7491-1910","authenticated-orcid":false,"given":"Silvia","family":"Guzm\u00e1n-Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-3879","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Flores-Flores","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Rosas-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"},{"name":"Department of Molecular Biomedicine, Centro de Investigaci\u00f3n y de Estudios Avanzados, Mexico City 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-5631","authenticated-orcid":false,"given":"Teresa","family":"Santos-Mendoza","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"de las Rivas, J., and Fontanillo, C. (2010). Protein-protein interactions essentials: Key concepts to building and analyzing interactome networks. PLoS Comput. Biol., 6.","DOI":"10.1371\/journal.pcbi.1000807"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/147648","article-title":"Protein-Protein Interaction Detection: Methods and Analysis","volume":"2014","author":"Rao","year":"2014","journal-title":"Int. J. Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6959","DOI":"10.1073\/pnas.0708078105","article-title":"Estimating the size of the human interactome","volume":"105","author":"Stumpf","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1073\/pnas.1312296111","article-title":"Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes","volume":"111","author":"Ivarsson","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1800143","DOI":"10.1002\/adtp.201800143","article-title":"PDZ Domains as Drug Targets","volume":"2","author":"Christensen","year":"2019","journal-title":"Adv. Ther. (Weinh)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41392-020-00315-3","article-title":"Recent advances in the development of protein\u2013protein interactions modulators: Mechanisms and clinical trials","volume":"5","author":"Lu","year":"2020","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3390\/membranes5040597","article-title":"Membrane binding and modulation of the PDZ domain of PICK1","volume":"5","author":"Erlendsson","year":"2015","journal-title":"Membranes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.chembiol.2011.06.013","article-title":"A systematic family-wide investigation reveals that \u223c30% of mammalian PDZ domains engage in PDZ-PDZ interactions","volume":"18","author":"Chang","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1073\/pnas.0902225107","article-title":"Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD","volume":"107","author":"Thorsen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","first-page":"100022","article-title":"Specificity in PDZ-peptide interaction networks: Computational analysis and review","volume":"4","author":"Amacher","year":"2020","journal-title":"J. Struct. Biol. X"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1111\/j.1742-4658.2006.05521.x","article-title":"Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide","volume":"273","author":"Oksanen","year":"2006","journal-title":"FEBS J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0968-0004(90)90019-8","article-title":"Peptide sequences that target cytosolic proteins for lysosomal proteolysis","volume":"15","author":"Dice","year":"1990","journal-title":"Trends Biochem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/S1097-2765(02)00549-X","article-title":"PIP2-PDZ Domain Binding Controls the Association of Syntenin with the Plasma Membrane","volume":"9","author":"Zimmermann","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1016\/j.febslet.2012.04.015","article-title":"Plasticity of PDZ domains in ligand recognition and signaling","volume":"586","author":"Ivarsson","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/sj.onc.1201567","article-title":"The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins","volume":"16","author":"Rousset","year":"1998","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.1073\/pnas.94.13.6670","article-title":"Binding of human virus oncoproteins to hDlg\/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein","volume":"94","author":"Lee","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11612","DOI":"10.1073\/pnas.94.21.11612","article-title":"Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein","volume":"94","author":"Kiyono","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.neuro.24.1.1","article-title":"PDZ Domains and the Organization of Supramolecular Complexes","volume":"24","author":"Sheng","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1016\/j.jmb.2018.04.016","article-title":"Upsetting the Balance: When Viruses Manipulate Cell Polarity Control","volume":"430","author":"Thomas","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tonikian, R., Zhang, Y., Sazinsky, S.L., Currell, B., Yeh, J., Reva, B., Held, H.A., Appleton, B.A., Evangelista, M., and Wu, Y. (2008). A Specificity Map for the PDZ Domain Family. PLoS Biol., 6.","DOI":"10.1371\/journal.pbio.0060239"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11544","DOI":"10.1128\/JVI.05410-11","article-title":"Emerging Theme: Cellular PDZ Proteins as Common Targets of Pathogenic Viruses","volume":"85","author":"Javier","year":"2011","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10607","DOI":"10.1096\/fj.201900518R","article-title":"Viral targeting of PDZ polarity proteins in the immune system as a potential evasion mechanism","volume":"33","year":"2019","journal-title":"FASEB J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1002\/pro.3741","article-title":"MotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity","volume":"28","author":"Valgardson","year":"2019","journal-title":"Protein Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8896","DOI":"10.1002\/anie.201412070","article-title":"Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes","volume":"54","author":"Glas","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/pro.3361","article-title":"Lock and chop: A novel method for the generation of a PICK1 PDZ domain and piperidine-based inhibitor co-crystal structure","volume":"27","author":"Marcotte","year":"2018","journal-title":"Protein Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Shepley-McTaggart, A., Sagum, C.A., Oliva, I., Rybakovsky, E., DiGuilio, K., Liang, J., Bedford, M.T., Cassel, J., Sudol, M., and Mullin, J.M. (2021). SARS-CoV-2 Envelope (E) protein interacts with PDZ-domain-2 of host tight junction protein ZO1. PLoS ONE, 16.","DOI":"10.1101\/2020.12.22.422708"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1111\/bph.15084","article-title":"nNOS-CAPON blockers produce anxiolytic effects by promoting synaptogenesis in chronic stress-induced animal models of anxiety","volume":"177","author":"Zhu","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41419-019-1802-z","article-title":"Modifying PTEN recruitment promotes neuron survival, regeneration, and functional recovery after CNS injury","volume":"10","author":"Shabanzadeh","year":"2019","journal-title":"Cell Death Dis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ra5","DOI":"10.1126\/scisignal.2000510","article-title":"Attenuation of Rabies Virulence: Takeover by the Cytoplasmic Domain of Its Envelope Protein","volume":"3","author":"Prehaud","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13755","DOI":"10.1074\/jbc.RA119.008238","article-title":"Structure-based optimization of a PDZ-binding motif within a viral peptide stimulates neurite outgrowth","volume":"294","author":"Khan","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1016\/j.bmc.2017.06.052","article-title":"Therapeutic peptides: Historical perspectives, current development trends, and future directions","volume":"26","author":"Lau","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/aps.2018.5","article-title":"Discovery and development of NA-1 for the treatment of acute ischemic stroke","volume":"39","author":"Ballarin","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yeh, C.Y., Schulien, A.J., Molyneaux, B.J., and Aizenman, E. (2020). Lessons from recent advances in ischemic stroke management and targeting kv2.1 for neuroprotection. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202008.0094.v1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nchembio.152","article-title":"Inhibition of Wntsignaling by Dishevelled PDZ peptides","volume":"5","author":"Zhang","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15252\/emmm.201911248","article-title":"A high-affinity, bivalent PDZ domain inhibitor complexes PICK 1 to alleviate neuropathic pain","volume":"12","author":"Christensen","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12074","DOI":"10.1021\/ja035540l","article-title":"A selective irreversible inhibitor targeting a PDZ protein interaction domain","volume":"125","author":"Fujii","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hill, M.D., Goyal, M., Menon, B.K., Nogueira, R.G., McTaggart, R.A., Demchuk, A.M., Poppe, A.Y., Buck, B.H., Field, T.S., and Dowlatshahi, D. (2020). Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): A multicentre, double-blind, randomised controlled trial. Lancet, 395.","DOI":"10.1016\/S0140-6736(20)30258-0"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5744","DOI":"10.1074\/jbc.M111.315762","article-title":"A chemokine receptor CXCR2 macromolecular complex regulates neutrophil functions in inflammatory diseases","volume":"287","author":"Wu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ejmech.2018.05.015","article-title":"Syntenin-targeted peptide blocker inhibits progression of cancer cells","volume":"154","author":"Liu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1073\/pnas.1616100114","article-title":"Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9\/Syntenin","volume":"114","author":"Kegelman","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.autrev.2017.12.004","article-title":"Clinical and experimental evidence for targeting CD6 in immune-based disorders","volume":"17","author":"Lin","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_43","first-page":"1","article-title":"CD6, a rheostat-type signalosome that tunes T cell activation","volume":"9","author":"Henriques","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1126\/science.1059157","article-title":"Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein","volume":"293","author":"Geijsen","year":"2001","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1182\/blood-2009-03-208850","article-title":"Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output","volume":"114","author":"Beekman","year":"2009","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/ncb3413","article-title":"An interaction between Scribble and the NADPH oxidase complex controls M1 macrophage polarization and function","volume":"18","author":"Zheng","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1161\/01.ATV.0000097769.47306.12","article-title":"Regulation of Superoxide Anion Production by NADPH Oxidase in Monocytes\/Macrophages","volume":"24","author":"Cathcart","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1006\/bbrc.2000.2897","article-title":"Activation of NADPH Oxidase in Alzheimer\u2019s Disease Brains","volume":"273","author":"Shimohama","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1096\/fj.03-0983fje","article-title":"Neuroprotective effect of dextromethorphan in the MPTP Parkinson\u2019s disease model: Role of NADPH oxidase","volume":"18","author":"Zhang","year":"2004","journal-title":"FASEB J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100881","DOI":"10.1016\/j.jbc.2021.100881","article-title":"Human GPR17 missense variants identified in metabolic disease patients have distinct downstream signaling profiles","volume":"297","author":"Conley","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.coemr.2020.06.007","article-title":"Calcium-sensing receptor signaling\u2014How human disease informs biology","volume":"16","author":"Gorvin","year":"2021","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e21719","DOI":"10.1096\/fj.202100070R","article-title":"A novel role of ADGRF1 (GPR110) in promoting cellular quiescence and chemoresistance in human epidermal growth factor receptor 2-positive breast cancer","volume":"35","author":"Abdulkareem","year":"2021","journal-title":"FASEB J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1124\/mol.115.098509","article-title":"PDZ protein regulation of g protein-coupled receptor trafficking and signaling pathways","volume":"88","author":"Dunn","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/celldisc.2015.11","article-title":"Individual protomers of a G protein-coupled receptor dimer integrate distinct functional modules","volume":"1","author":"Camp","year":"2015","journal-title":"Cell Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1152\/ajpregu.00738.2001","article-title":"Chemokines and chemokine receptors in leukocyte trafficking","volume":"283","author":"Olson","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liu, J., Li, S., Liu, J., Liang, B., Wang, X., Wang, H., Li, W., Tong, Q., Yi, J., and Zhao, L. (2020). Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine, 55.","DOI":"10.1016\/j.ebiom.2020.102763"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ajpath.2020.08.009","article-title":"Immunopathology of Hyperinflammation in COVID-19","volume":"191","author":"Gustine","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.3389\/fonc.2019.01146","article-title":"Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy","volume":"9","author":"Masucci","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lu, G., Wu, Y., Jiang, Y., Wang, S., Hou, Y., Guan, X., Brunzelle, J., Sirinupong, N., Sheng, S., and Li, C. (2013). Structural Insights into Neutrophilic Migration Revealed by the Crystal Structure of the Chemokine Receptor CXCR2 in Complex with the First PDZ Domain of NHERF1. PLoS ONE, 8.","DOI":"10.2210\/pdb4jl7\/pdb"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"30868","DOI":"10.1074\/jbc.M804054200","article-title":"The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis","volume":"283","author":"Baugher","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1593\/tlo.13133","article-title":"CXCR2 macromolecular complex in pancreatic cancer: A potential therapeutic target in tumor growth","volume":"6","author":"Wang","year":"2013","journal-title":"Transl. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.scr.2014.12.001","article-title":"A critical role of CXCR2 PDZ-mediated interactions in endothelial progenitor cell homing and angiogenesis","volume":"14","author":"Hou","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1517\/13543776.2014.887682","article-title":"CXCR2 modulators: A patent review (2009\u20132013)","volume":"24","author":"Dwyer","year":"2014","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/cmdc.201800027","article-title":"Synthesis, Structure-activity Relationship Studies and ADMET Properties of 3-aminocyclohex-2-en-1-ones as Chemokine Receptor 2 (CXCR2) Antagonists","volume":"13","author":"Dai","year":"2018","journal-title":"ChemMedChem"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1084\/jem.20201342","article-title":"Blocking inflammation on the way: Rationale for CXCR2 antagonists for the treatment of COVID-19","volume":"217","author":"Koenig","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.7150\/ijms.53564","article-title":"Role of IL-6 inhibitor in treatment of COVID-19-related cytokine release syndrome","volume":"18","author":"Du","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.pharmtox.48.113006.094646","article-title":"G protein-coupled receptor sorting to endosomes and lysosomes","volume":"48","author":"Marchese","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1681\/ASN.2009070741","article-title":"CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis","volume":"21","author":"Turner","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1084\/jem.20071397","article-title":"Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model","volume":"204","author":"Hirota","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kadomoto, S., Izumi, K., and Mizokami, A. (2020). The CCL20-CCR6 axis in cancer progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155186"},{"key":"ref_71","first-page":"571","article-title":"Regulation and biological functions of the CX3CL1-CX3CR1 axis and its relevance in solid cancer: A mini-review","volume":"12","year":"2020","journal-title":"J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Cormican, S., and Griffin, M.D. (2021). Fractalkine (CX3CL1) and Its Receptor CX3CR1: A Promising Therapeutic Target in Chronic Kidney Disease?. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.664202"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13683","DOI":"10.1073\/pnas.94.25.13683","article-title":"Syntenin, a PDZ protein that binds syndecan cytoplasmic domains","volume":"94","author":"Grootjans","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1091\/mbc.12.2.339","article-title":"Characterization of Syntenin, a Syndecan-binding PDZ Protein, as a Component of Cell Adhesion Sites and Microfilaments","volume":"12","author":"Zimmermann","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/ncb2502","article-title":"Syndecan-syntenin-ALIX regulates the biogenesis of exosomes","volume":"14","author":"Baietti","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1242\/jcs.026401","article-title":"The ins and outs of syntenin, a multifunctional intracellular adaptor protein","volume":"121","author":"Beekman","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Shimada, T., Yasuda, S., Sugiura, H., and Yamagata, K. (2019). Syntenin: PDZ Protein Regulating Signaling Pathways and Cellular Functions. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174171"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6781","DOI":"10.1038\/s41388-019-0920-5","article-title":"Regulation of neuroblastoma migration, invasion, and in vivo metastasis by genetic and pharmacological manipulation of MDA-9\/Syntenin","volume":"38","author":"Bhoopathi","year":"2019","journal-title":"Oncogene"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s10555-020-09886-7","article-title":"MDA-9\/Syntenin\/SDCBP: New insights into a unique multifunctional scaffold protein","volume":"39","author":"Pradhan","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1873-3468.12037","article-title":"Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin","volume":"590","author":"Garg","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1158\/1535-7163.MCT-18-1019","article-title":"Suppression of prostate cancer pathogenesis using an MDA-9\/syntenin (SDCBP) Pdz1 small-molecule inhibitor","volume":"18","author":"Das","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"104695","DOI":"10.1016\/j.phrs.2020.104695","article-title":"MDA-9\/Syntenin (SDCBP): Novel gene and therapeutic target for cancer metastasis","volume":"155","author":"Das","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10549-018-4833-8","article-title":"Syntenin1\/MDA-9 (SDCBP) induces immune evasion in triple-negative breast cancer by upregulating PD-L1","volume":"171","author":"Liu","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1242\/jcs.094912","article-title":"Association of syntenin-1 with M-RIP polarizes Rac-1 activation during chemotaxis and immune interactions","volume":"125","author":"Tejera","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.4049\/jimmunol.175.3.1406","article-title":"The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains","volume":"175","author":"Gimferrer","year":"2005","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Mori, D., Gr\u00e9goire, C., Voisinne, G., Celis-Gutierrez, J., Aussel, R., Girard, L., Camus, M., Marcellin, M., Argenty, J., and Burlet-Schiltz, O. (2021). The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation. J. Exp. Med., 218.","DOI":"10.1084\/jem.20201011"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Rodrigo-Mu\u00f1oz, J.M., Gil-Mart\u00ednez, M., Sastre, B., and del Pozo, V. (2021). Emerging Evidence for Pleiotropism of Eosinophils. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137075"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1164\/rccm.200307-1024OC","article-title":"Kinetics of Bone Marrow Eosinophilopoiesis and Associated Cytokines after Allergen Inhalation","volume":"169","author":"Dorman","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fmicb.2013.00263","article-title":"Pathology of asthma","volume":"4","author":"Kudo","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.jaci.2018.01.008","article-title":"Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma","volume":"141","author":"Sehmi","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Herb, M., Schramm, M., and Filosa, S. (2021). Functions of ROS in Macrophages and Antimicrobial Immunity. Antioxidants, 10.","DOI":"10.3390\/antiox10020313"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.freeradbiomed.2010.07.027","article-title":"Nox enzymes from fungus to fly to fish and what they tell us about Nox function in mammals","volume":"49","author":"Aguirre","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-pathol-012513-104651","article-title":"Nox enzymes and new thinking on reactive oxygen: A double-edged sword revisited","volume":"9","author":"Lambeth","year":"2014","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.freeradbiomed.2010.09.016","article-title":"Intracellular generation of superoxide by the phagocyte NADPH oxidase: How, where, and what for?","volume":"49","author":"Bylund","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"46065","DOI":"10.1074\/jbc.M403046200","article-title":"NOX3, a superoxide-generating NADPH oxidase of the inner ear","volume":"279","author":"Malgrange","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1152\/ajpheart.00242.2010","article-title":"Upregulation of Nox1 in vascular smooth muscle leads to impaired endothelium-dependent relaxation via eNOS uncoupling","volume":"299","author":"Dikalova","year":"2010","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1016\/j.freeradbiomed.2010.09.027","article-title":"Urothelial cells produce hydrogen peroxide through the activation of Duox1","volume":"49","author":"Ruisanchez","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.febslet.2005.12.049","article-title":"Decreased blood pressure in NOX1-deficient mice","volume":"580","author":"Gavazzi","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1089\/ars.2013.5814","article-title":"Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement","volume":"23","author":"Radermacher","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1093\/cvr\/cvz183","article-title":"New opportunities for targeting redox dysregulation in cardiovascular disease","volume":"116","author":"Bubb","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1089\/ars.2013.5607","article-title":"NADPH Oxidases in Vascular Pathology","volume":"20","author":"Konior","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/cvr\/cvx108","article-title":"The role of infiltrating immune cells in dysfunctional adipose tissue","volume":"113","author":"Guzik","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1111\/bph.13705","article-title":"Perivascular adipose tissue inflammation in vascular disease","volume":"174","author":"Nosalski","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41569-019-0260-8","article-title":"NADPH oxidases and oxidase crosstalk in cardiovascular diseases: Novel therapeutic targets","volume":"17","author":"Zhang","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1161\/CIRCULATIONAHA.112.132159","article-title":"NADPH Oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis","volume":"127","author":"Gray","year":"2013","journal-title":"Circulation"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2174\/1389450054021927","article-title":"NAD(P)H Oxidase Activation: A Potential Target Mechanism for Diabetic Vascular Complications, Progressive \u03b2-Cell Dysfunction and Metabolic Syndrome","volume":"6","author":"Inoguchi","year":"2005","journal-title":"Curr. Drug Targets"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/j.1476-5381.2011.01249.x","article-title":"NOX1, 2, 4, 5: Counting out oxidative stress","volume":"164","author":"Wingler","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1080\/1521654031000153049","article-title":"A Role for NOX NADPH Oxidases in Alzheimer\u2019s Disease and Other Types of Dementia?","volume":"55","author":"Zekry","year":"2003","journal-title":"IUBMB Life (Int. Union Biochem. Mol. Biol. Life)"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1523\/JNEUROSCI.5207-04.2005","article-title":"NADPH Oxidase-Derived Reactive Oxygen Species Mediate the Cerebrovascular Dysfunction Induced by the Amyloid Peptide","volume":"25","author":"Park","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Block, M.L. (2008). NADPH oxidase as a therapeutic target in Alzheimer\u2019s disease. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-S2-S8"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.neurobiolaging.2005.09.036","article-title":"A key role for the microglial NADPH oxidase in APP-dependent killing of neurons","volume":"27","author":"Qin","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1189\/jlb.1112603","article-title":"A leading role for the immune system in the pathophysiology of preeclampsia","volume":"94","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1055\/s-2007-1016254","article-title":"Oxidative Stress and Altered Endothelial Cell Function in Preeclampsia","volume":"16","author":"Davidge","year":"1998","journal-title":"Semin. Reprod. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"H24","DOI":"10.1152\/ajpheart.00799.2009","article-title":"Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE\u2212\/\u2212 mice","volume":"298","author":"Judkins","year":"2010","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"86.e1","DOI":"10.1016\/j.ajog.2014.07.021","article-title":"Activin and NADPH-oxidase in preeclampsia: Insights from in vitro and murine studies","volume":"212","author":"Lim","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"E5308","DOI":"10.1073\/pnas.1514161113","article-title":"Binding of EBP50 to Nox organizing subunit p47phox is pivotal to cellular reactive species generation and altered vascular phenotype","volume":"113","author":"Ghouleh","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:20:31Z","timestamp":1760167231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,21]]},"references-count":117,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26216367"],"URL":"https:\/\/doi.org\/10.3390\/molecules26216367","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,21]]}}}