{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:15:46Z","timestamp":1780316146570,"version":"3.54.1"},"reference-count":28,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.ejmech.2020.112515","type":"journal-article","created":{"date-parts":[[2020,6,21]],"date-time":"2020-06-21T10:21:17Z","timestamp":1592734877000},"page":"112515","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"special_numbering":"C","title":["Targeting fungal virulence factor by small molecules: Structure-based discovery of novel secreted aspartic protease 2 (SAP2) inhibitors"],"prefix":"10.1016","volume":"201","author":[{"given":"Chenglan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanchao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunquan","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2020.112515_bib1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejmech.2020.112515_bib2","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1126\/science.aap7999","article-title":"Worldwide emergence of resistance to antifungal drugs challenges human health and food security","volume":"360","author":"Fisher","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2020.112515_bib3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ijantimicag.2017.05.019","article-title":"Epidemiology of antifungal resistance in human pathogenic yeasts: current viewpoint and practical recommendations for management","volume":"50","author":"Farmakiotis","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"10.1016\/j.ejmech.2020.112515_bib4","doi-asserted-by":"crossref","first-page":"300","DOI":"10.15698\/mic2018.07.638","article-title":"Methodologies for in\u00a0vitro and in\u00a0vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms","volume":"5","author":"Van Dijck","year":"2018","journal-title":"Microb.Cell"},{"key":"10.1016\/j.ejmech.2020.112515_bib5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1439-0507.2005.01165.x","article-title":"Hydrolytic enzymes as virulence factors of Candida albicans","volume":"48","author":"Schaller","year":"2005","journal-title":"Mycoses"},{"key":"10.1016\/j.ejmech.2020.112515_bib6","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1128\/CMR.13.1.122","article-title":"Potential role of phospholipases in virulence and fungal pathogenesis","volume":"13","author":"Ghannoum","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.ejmech.2020.112515_bib7","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/omi.12206","article-title":"Extracellular proteinases of Candida species pathogenic yeasts","volume":"33","author":"Rapala-Kozik","year":"2018","journal-title":"Mol. Oral Microbiol."},{"key":"10.1016\/j.ejmech.2020.112515_bib8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s12223-014-0368-5","article-title":"Two SAPP2 gene homologs are present in Candida parapsilosis genome","volume":"60","author":"Dost\u00e1l","year":"2015","journal-title":"Folia Microbiol."},{"key":"10.1016\/j.ejmech.2020.112515_bib9","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/infdis\/jir873","article-title":"The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence","volume":"205","author":"Horv\u00e1th","year":"2012","journal-title":"J.\u00a0Infect. Dis."},{"key":"10.1016\/j.ejmech.2020.112515_bib10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1128\/IAI.69.1.405-412.2001","article-title":"Secreted aspartic proteinase family of Candida tropicalis","volume":"69","author":"Zaugg","year":"2001","journal-title":"Infect. Immun."},{"key":"10.1016\/j.ejmech.2020.112515_bib11","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1590\/S0074-02762009000300018","article-title":"Phylogeny and evolution of the aspartyl protease family from clinically relevant Candida species","volume":"104","author":"Parra-Ortega","year":"2009","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"10.1016\/j.ejmech.2020.112515_bib12","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/jb\/mvr073","article-title":"Comprehensive characterization of secreted aspartic proteases encoded by a virulence gene family in Candida albicans","volume":"150","author":"Aoki","year":"2011","journal-title":"J.\u00a0Biochem."},{"key":"10.1016\/j.ejmech.2020.112515_bib13","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/jam.13745","article-title":"Dermaseptin-S1 decreases Candida albicans growth, biofilm formation and the expression of hyphal wall protein 1 and aspartic protease genes","volume":"125","author":"Belmadani","year":"2018","journal-title":"J.\u00a0Appl. Microbiol."},{"key":"10.1016\/j.ejmech.2020.112515_bib14","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1021\/acs.jmedchem.8b01598","article-title":"Discovery of carboline derivatives as potent antifungal agents for the treatment of Cryptococcal meningitis","volume":"62","author":"Tu","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112515_bib15","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.ejmech.2017.10.043","article-title":"Discovery of simplified sampangine derivatives as novel fungal biofilm inhibitors","volume":"143","author":"Liu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112515_bib16","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1021\/acs.jmedchem.7b01413","article-title":"Emerging new targets for the treatment of resistant fungal infections","volume":"61","author":"Liu","year":"2018","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112515_bib17","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1021\/acs.jmedchem.6b01203","article-title":"Tackling fungal resistance by biofilm inhibitors","volume":"60","author":"Wu","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112515_bib18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1439-0507.2009.01793.x","article-title":"Enhancement of Secretory Aspartyl Protease production in biofilms of Candida albicans exposed to sub-inhibitory concentrations of fluconazole","volume":"54","author":"Mores","year":"2011","journal-title":"Mycoses"},{"key":"10.1016\/j.ejmech.2020.112515_bib19","doi-asserted-by":"crossref","first-page":"13535","DOI":"10.1039\/C8CC07810F","article-title":"Novel non-peptidic small molecule inhibitors of secreted aspartic protease 2 (SAP2) for the treatment of resistant fungal infections","volume":"54","author":"Dong","year":"2018","journal-title":"Chem. Commun."},{"key":"10.1016\/j.ejmech.2020.112515_bib20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/cmdc.201000370","article-title":"New cis-configured aziridine-2-carboxylates as aspartic acid protease inhibitors","volume":"6","author":"B\u00fcchold","year":"2011","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2020.112515_bib21","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/cmdc.200700101","article-title":"Cis-configured aziridines are new pseudo-irreversible dual-mode inhibitors of Candida albicans secreted aspartic protease 2","volume":"3","author":"Degel","year":"2008","journal-title":"ChemMedChem: Chemistry Enabling Drug Discovery"},{"key":"10.1016\/j.ejmech.2020.112515_bib22","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/abio.1998.3014","article-title":"Use of a fluorescence plate reader for measuring kinetic parameters with inner filter effect correction","volume":"267","author":"Liu","year":"1999","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ejmech.2020.112515_bib23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/0003-2697(92)90145-W","article-title":"Application of a fluorogenic substrate in the assay of proteolytic activity and in the discovery of a potent inhibitor of Candida albicans aspartic proteinase","volume":"204","author":"Capobianco","year":"1992","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ejmech.2020.112515_bib24","unstructured":"Birchmeier, Walter; Rademann, Joerg; Grosskopf, Stefanie.WO. Patent 128909, Dec 7, 2006."},{"key":"10.1016\/j.ejmech.2020.112515_bib25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/CMR.15.2.167-193.2002","article-title":"Biofilms: survival mechanisms of clinically relevant microorganisms","volume":"15","author":"Donlan","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.ejmech.2020.112515_bib26","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1128\/AAC.01583-13","article-title":"In\u00a0vitro and in\u00a0vivo activities of pterostilbene against Candida albicans biofilms","volume":"58","author":"Li","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2020.112515_bib27","doi-asserted-by":"crossref","first-page":"14648","DOI":"10.1039\/C5CC05699C","article-title":"The discovery of novel antifungal scaffolds by structural simplification of the natural product sampangine","volume":"51","author":"Jiang","year":"2015","journal-title":"Chem. Commun. (Camb)"},{"key":"10.1016\/j.ejmech.2020.112515_bib28","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nrmicro2636","article-title":"Growth of Candida albicans hyphae","volume":"9","author":"Sudbery","year":"2011","journal-title":"Nat. Rev. Microbiol."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523420304876?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523420304876?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:13:50Z","timestamp":1759328030000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523420304876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":28,"alternative-id":["S0223523420304876"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2020.112515","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting fungal virulence factor by small molecules: Structure-based discovery of novel secreted aspartic protease 2 (SAP2) inhibitors","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2020.112515","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"112515"}}