{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:48:37Z","timestamp":1765961317183,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major State Special Research Project of China","award":["2016YFA0101200"],"award-info":[{"award-number":["2016YFA0101200"]}]},{"DOI":"10.13039\/501100012336","name":"Major State Basic Research Development Program of China","doi-asserted-by":"publisher","award":["973 Program, 2015CB553701"],"award-info":[{"award-number":["973 Program, 2015CB553701"]}],"id":[{"id":"10.13039\/501100012336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21778050","91749125"],"award-info":[{"award-number":["21778050","91749125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anhui Key Research and Development Program","award":["201904a07020092"],"award-info":[{"award-number":["201904a07020092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis. Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors. However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation. In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays. Four compounds were screened as potential CD147 glycosylation inhibitors. Of these, compound 72 was finally identified as the best candidate. Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line. Results further suggest that compound 72 could promote the expression of E-cadherin by targeting CD147, thereby inhibiting tumor migration. Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.<\/jats:p>","DOI":"10.3390\/molecules26010033","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T12:19:51Z","timestamp":1608725991000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-5802","authenticated-orcid":false,"given":"Wenqian","family":"Li","sequence":"first","affiliation":[{"name":"Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daojiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yushu","family":"Ge","sequence":"additional","affiliation":[{"name":"Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nrc.2016.25","article-title":"Targeting metastasis","volume":"16","author":"Steeg","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.apsb.2015.07.005","article-title":"Cancer metastases: Challenges and opportunities","volume":"5","author":"Guan","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.cell.2016.11.037","article-title":"Emerging Biological Principles of Metastasis","volume":"168","author":"Lambert","year":"2017","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.3802\/jgo.2016.27.e43","article-title":"Advances in diagnosis and treatment of metastatic cervical cancer","volume":"27","author":"Li","year":"2016","journal-title":"J. Gynecol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/nm.3391","article-title":"Tumor metastasis: Moving new biological insights into the clinic","volume":"19","author":"Wan","year":"2013","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35478","DOI":"10.18632\/oncotarget.8155","article-title":"Hallmarks of glycosylation in cancer","volume":"7","author":"Munkley","year":"2016","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.sbi.2011.08.005","article-title":"Mechanisms and principles of N-linked protein glycosylation","volume":"21","author":"Schwarz","year":"2011","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1126\/science.291.5512.2364","article-title":"Intracellular functions of N-linked glycans","volume":"291","author":"Helenius","year":"2001","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ymeth.2006.10.002","article-title":"Scanning N-glycosylation mutagenesis of membrane proteins","volume":"41","author":"Cheung","year":"2007","journal-title":"Methods"},{"key":"ref_12","first-page":"434","article-title":"The Human Tumor Cell-derived Collagenase Stimulatory Factor (Renamed EMMPRIN) Is a Member of the Immunoglobulin Superfamily","volume":"55","author":"Biswas","year":"1995","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1093\/oxfordjournals.jbchem.a123657","article-title":"The basigin group of the immunoglobulin superfamily: Complete conservation of a segment in and around transmembrane domains of human and mouse basigin and chicken HT7 antigen","volume":"110","author":"Miyauchi","year":"1991","journal-title":"J. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.3892\/etm.2017.4818","article-title":"Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma","volume":"14","author":"Xiao","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_15","first-page":"4280","article-title":"CD147 promotes cervical cancer migration and invasion by up-regulating fatty acid synthase expression","volume":"12","author":"Guo","year":"2019","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/B978-0-12-800092-2.00013-7","article-title":"CD147: Regulator of Hyaluronan Signaling in Invasiveness and Chemoresistance","volume":"123","author":"Grass","year":"2014","journal-title":"Hyaluronan Signal. Turnover"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1158\/0008-5472.CAN-11-3843","article-title":"S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis","volume":"73","author":"Hibino","year":"2013","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.yexmp.2007.08.014","article-title":"CD147 immunoglobulin superfamily receptor function and role in pathology","volume":"83","author":"Iacono","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep32804","article-title":"CD147\/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis","volume":"6","author":"Xin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1365-2559.2009.03280.x","article-title":"HAb18G (CD147), a cancer-associated biomarker and its role in cancer detection","volume":"54","author":"Li","year":"2009","journal-title":"Histopathology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17411","DOI":"10.3390\/ijms151017411","article-title":"The biological function and clinical utilization of CD147 in human diseases: A review of the current scientific literature","volume":"15","author":"Xiong","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_22","first-page":"429","article-title":"RNA interference targeting extracellular matrix metalloproteinase inducer (CD147) inhibits growth and increases chemosensitivity in human cervical cancer cells","volume":"34","author":"Zhang","year":"2013","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1002\/ijc.22062","article-title":"High incidence of EMMPRIN expression in human tumors","volume":"119","author":"Riethdorf","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Landras, A., de Moura, C.R., Jouenne, F., Lebbe, C., Menashi, S., and Mourah, S. (2019). CD147 is a promising target of tumor progression and a prognostic biomarker. Cancers, 11.","DOI":"10.3390\/cancers11111803"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/cbin.10104","article-title":"RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9","volume":"37","author":"Fan","year":"2013","journal-title":"Cell Biol. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/path.5054","article-title":"N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147\/basigin with integrin \u03b21 and promotes HCC metastasis","volume":"245","author":"Cui","year":"2018","journal-title":"J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrc3982","article-title":"Glycosylation in cancer: Mechanisms and clinical implications","volume":"15","author":"Pinho","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6356","DOI":"10.3390\/ijms15046356","article-title":"Importance of N-glycosylation on CD147 for its biological functions","volume":"15","author":"Bai","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4668","DOI":"10.1091\/mbc.e12-06-0428","article-title":"Unassembled CD147 is an endogenous endoplasmic reticulum-associated degradation substrate","volume":"23","author":"Tyler","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1042\/BJ20120343","article-title":"Modulation of CD147-induced matrix metalloproteinase activity: Role of CD147 N-glycosylation","volume":"449","author":"Huang","year":"2013","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/hep.21465","article-title":"A randomized controlled trial of licartin for preventing hepatoma recurrence after liver transplantation","volume":"45","author":"Xu","year":"2007","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10585-014-9689-7","article-title":"A chimeric antibody targeting CD147 inhibits hepatocellular carcinoma cell motility via FAK-PI3K-Akt-Girdin signaling pathway","volume":"32","author":"Wang","year":"2015","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9429","DOI":"10.18632\/oncotarget.6990","article-title":"A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells","volume":"7","author":"Fu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26812","DOI":"10.1016\/S0021-9258(19)61448-1","article-title":"3\u2019-Azidothymidine potently inhibits the biosynthesis of highly branched N-linked oligosaccharides and poly-N-acetyllactosamine chains in cells","volume":"275","author":"Steet","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.3892\/mmr.2015.3241","article-title":"3\u2019-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells","volume":"11","author":"Xu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1091\/mbc.e04-05-0402","article-title":"Links between CD147 function, glycosylation, and caveolin-1","volume":"15","author":"Tang","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural Products as Sources of New Drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1016\/j.bbagen.2013.02.008","article-title":"Natural products: A continuing source of novel drug leads","volume":"1830","author":"Cragg","year":"2013","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1021\/acs.joc.5b00384","article-title":"Enantioselective syntheses of spiroketals via a tandem reaction of Cu(I)-catalyzed cycloetherification and hydrogen-bond-induced [4 + 2] cyclization","volume":"80","author":"Tian","year":"2015","journal-title":"J. Org. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1021\/ol502258n","article-title":"Iminoxyl radical-promoted dichotomous cyclizations: Efficient oxyoximation and aminooximation of alkenes","volume":"16","author":"Peng","year":"2014","journal-title":"Org. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1479-5876-12-190","article-title":"Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma","volume":"12","author":"Wu","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1160\/TH04-08-0536","article-title":"Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression","volume":"93","author":"Yan","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ijpharm.2011.03.053","article-title":"The MTT assay as tool to evaluate and compare excipient toxicity in vitro on respiratory epithelial cells","volume":"411","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35210","DOI":"10.1038\/srep35210","article-title":"N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: Promoting tumour metastasis in hepatocellular carcinoma","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrc.2017.118","article-title":"EMT in cancer","volume":"18","author":"Brabletz","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3109\/03008207.2015.1060970","article-title":"The role of EMT and MET in cancer dissemination","volume":"56","author":"Banyard","year":"2015","journal-title":"Connect. Tissue Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.canlet.2012.09.025","article-title":"Why does cancer therapy lack effective anti-metastasis drugs?","volume":"328","author":"Weber","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.1074\/jbc.271.11.6363","article-title":"The Amino Acid at the X Position of an Asn-X-Ser Sequon Is an Important Determinant of N-Linked Core-glycosylation Efficiency","volume":"271","author":"Shakineshleman","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-61779-108-6_2","article-title":"Mammalian Cell Viability","volume":"740","author":"Louis","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/protein\/8.2.127","article-title":"Ligplot: A program to generate schematic diagrams of protein-ligand interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Protein Eng. Des. Sel."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/33\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:59Z","timestamp":1760179739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,23]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["molecules26010033"],"URL":"https:\/\/doi.org\/10.3390\/molecules26010033","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2020,12,23]]}}}