{"id":"https://openalex.org/W3110949050","doi":"https://doi.org/10.1021/acsmedchemlett.0c00422","title":"Design and Synthesis of Fragment Derivatives with a Unique Inhibition Mechanism of the uPAR\u00b7uPA Interaction","display_name":"Design and Synthesis of Fragment Derivatives with a Unique Inhibition Mechanism of the uPAR\u00b7uPA Interaction","publication_year":2020,"publication_date":"2020-12-10","ids":{"openalex":"https://openalex.org/W3110949050","doi":"https://doi.org/10.1021/acsmedchemlett.0c00422","mag":"3110949050","pmid":"https://pubmed.ncbi.nlm.nih.gov/33488965","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/7812671"},"language":"en","primary_location":{"id":"doi:10.1021/acsmedchemlett.0c00422","doi":"https://doi.org/10.1021/acsmedchemlett.0c00422","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acsmedchemlett.0c00422","pdf_url":null,"source":{"id":"https://openalex.org/S191852912","display_name":"ACS Medicinal Chemistry Letters","issn_l":"1948-5875","issn":["1948-5875"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-1","ki-jl-1","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ACS Medicinal Chemistry Letters","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7812671","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5086068457","display_name":"Khuchtumur Bum\u2010Erdene","orcid":"https://orcid.org/0000-0003-3222-7384","observed_orcids":["https://orcid.org/0000-0003-3222-7384"]},"institutions":[{"id":"https://openalex.org/I4394709130","display_name":"Indiana University School of Medicine","ror":"https://ror.org/02ets8c94","country_code":"US","type":"education","lineage":["https://openalex.org/I4394709130","https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Khuchtumur Bum-Erdene","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States","institution_ids":["https://openalex.org/I4394709130"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040946263","display_name":"Degang Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4394709130","display_name":"Indiana University School of Medicine","ror":"https://ror.org/02ets8c94","country_code":"US","type":"education","lineage":["https://openalex.org/I4394709130","https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Degang Liu","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States","institution_ids":["https://openalex.org/I4394709130"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022469850","display_name":"David Daqiang Xu","orcid":"https://orcid.org/0000-0003-3949-0599","observed_orcids":["https://orcid.org/0000-0003-3949-0599"]},"institutions":[{"id":"https://openalex.org/I4394709130","display_name":"Indiana University School of Medicine","ror":"https://ror.org/02ets8c94","country_code":"US","type":"education","lineage":["https://openalex.org/I4394709130","https://openalex.org/I592451"]},{"id":"https://openalex.org/I55769427","display_name":"Indiana University \u2013 Purdue University Indianapolis","ror":"https://ror.org/05gxnyn08","country_code":"US","type":"education","lineage":["https://openalex.org/I55769427","https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Xu","raw_affiliation_strings":["Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States"],"raw_orcid":"https://orcid.org/0000-0003-3949-0599","affiliations":[{"raw_affiliation_string":"Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States","institution_ids":["https://openalex.org/I4394709130","https://openalex.org/I55769427"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028048039","display_name":"Mona K. Ghozayel","orcid":"https://orcid.org/0000-0002-5766-3214","observed_orcids":["https://orcid.org/0000-0002-5766-3214"]},"institutions":[{"id":"https://openalex.org/I4394709130","display_name":"Indiana University School of Medicine","ror":"https://ror.org/02ets8c94","country_code":"US","type":"education","lineage":["https://openalex.org/I4394709130","https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mona K. Ghozayel","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States","institution_ids":["https://openalex.org/I4394709130"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5055133888","display_name":"Samy O. Meroueh","orcid":"https://orcid.org/0000-0002-3948-7499","observed_orcids":["https://orcid.org/0000-0002-3948-7499"]},"institutions":[{"id":"https://openalex.org/I4394709130","display_name":"Indiana University School of Medicine","ror":"https://ror.org/02ets8c94","country_code":"US","type":"education","lineage":["https://openalex.org/I4394709130","https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Samy O. Meroueh","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States"],"raw_orcid":"https://orcid.org/0000-0002-3948-7499","affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States","institution_ids":["https://openalex.org/I4394709130"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5055133888"],"corresponding_institution_ids":["https://openalex.org/I4394709130"],"apc_list":{"value":5000,"currency":"USD","value_usd":5000},"apc_paid":null,"fwci":0.3957,"has_fulltext":false,"cited_by_count":7,"citation_normalized_percentile":{"value":0.48918002,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":87,"max":95},"biblio":{"volume":"12","issue":"1","first_page":"60","last_page":"66"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10620","display_name":"Protease and Inhibitor Mechanisms","score":0.9901999831199646,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10620","display_name":"Protease and Inhibitor Mechanisms","score":0.9901999831199646,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.0017000000225380063,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.0013000000035390258,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/upar","display_name":"uPAR","score":0.9629999995231628},{"id":"https://openalex.org/keywords/upa","display_name":"uPA","score":0.9959999918937683},{"id":"https://openalex.org/keywords/protein-protein-interaction-inhibition","display_name":"protein-protein interaction inhibition","score":0.8579999804496765},{"id":"https://openalex.org/keywords/fragment-based-drug-discovery","display_name":"fragment-based drug discovery","score":0.7850000262260437},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.6740000247955322},{"id":"https://openalex.org/keywords/serine-protease-inhibitors","display_name":"serine protease inhibitors","score":0.5370000004768372}],"concepts":[{"id":"https://openalex.org/C2776235265","wikidata":"https://www.wikidata.org/wiki/Q18392052","display_name":"Fragment (logic)","level":2,"score":0.8585952520370483},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.6756975054740906},{"id":"https://openalex.org/C56219504","wikidata":"https://www.wikidata.org/wiki/Q7900869","display_name":"Urokinase receptor","level":3,"score":0.5639535188674927},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.559817910194397},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.49049514532089233},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4574723243713379},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.4051809310913086},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.33424219489097595},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.23394042253494263},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.15326616168022156},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.1323150396347046},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.11976748704910278},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.07984939217567444},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.1021/acsmedchemlett.0c00422","doi":"https://doi.org/10.1021/acsmedchemlett.0c00422","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acsmedchemlett.0c00422","pdf_url":null,"source":{"id":"https://openalex.org/S191852912","display_name":"ACS Medicinal Chemistry Letters","issn_l":"1948-5875","issn":["1948-5875"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-1","ki-jl-1","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ACS Medicinal Chemistry Letters","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:7812671","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7812671","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ACS Med Chem Lett","raw_type":"Text"},{"id":"pmid:33488965","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/33488965","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ACS medicinal chemistry letters","raw_type":"Journal Article"},{"id":"pmh:oai:scholarworks.indianapolis.iu.edu:1805/32531","doi":null,"is_oa":false,"landing_page_url":"https://hdl.handle.net/1805/32531","pdf_url":null,"source":{"id":"https://openalex.org/S4306400987","display_name":"IUScholarWorks (Indiana University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I592451","host_organization_name":"Indiana University","host_organization_lineage":["https://openalex.org/I592451"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PMC","raw_type":"Article"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:7812671","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7812671","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"ACS Med Chem Lett","raw_type":"Text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.7246000170707703}],"study_designs":[],"awards":[{"id":"https://openalex.org/G6228518967","display_name":"Small-Molecule Antagonists of Ral GTPases in Cancer","funder_award_id":"R01CA197928","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G8949060725","display_name":null,"funder_award_id":"RSG-12-092-01-CDD","funder_id":"https://openalex.org/F4320306095","funder_display_name":"American Cancer Society"}],"funders":[{"id":"https://openalex.org/F4320306095","display_name":"American Cancer Society","ror":"https://ror.org/02e463172"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":29,"referenced_works":["https://openalex.org/W247657422","https://openalex.org/W1971831135","https://openalex.org/W1972230693","https://openalex.org/W1977826373","https://openalex.org/W1980849091","https://openalex.org/W1988882773","https://openalex.org/W1990221290","https://openalex.org/W1997375815","https://openalex.org/W2002072990","https://openalex.org/W2003593894","https://openalex.org/W2010031911","https://openalex.org/W2026666216","https://openalex.org/W2032610615","https://openalex.org/W2057938042","https://openalex.org/W2062403128","https://openalex.org/W2062695451","https://openalex.org/W2069846304","https://openalex.org/W2080047273","https://openalex.org/W2118659300","https://openalex.org/W2129986286","https://openalex.org/W2143415621","https://openalex.org/W2161156455","https://openalex.org/W2279867722","https://openalex.org/W2322259951","https://openalex.org/W2463036497","https://openalex.org/W2758868811","https://openalex.org/W2898602871","https://openalex.org/W2906608599","https://openalex.org/W2943512580"],"related_works":["https://openalex.org/W4297252939","https://openalex.org/W2419096704","https://openalex.org/W2604026727","https://openalex.org/W1995666546","https://openalex.org/W2082079038","https://openalex.org/W2014577485","https://openalex.org/W2074929393","https://openalex.org/W118698600","https://openalex.org/W2758868811","https://openalex.org/W2145208608"],"abstract_inverted_index":{"There":[0],"is":[1,142],"substantial":[2],"interest":[3],"in":[4],"the":[5,12,20,28,94,100,117,121,125,132,136,167],"development":[6],"of":[7,35,54,79,96,106,131],"small":[8],"molecules":[9],"that":[10,39,112,124,141],"inhibit":[11],"tight":[13],"and":[14,27,82,87],"highly":[15],"challenging":[16],"protein\u2013protein":[17],"interaction":[18],"between":[19],"glycophosphatidylinositol":[21],"(GPI)-anchored":[22],"cell":[23,168],"surface":[24],"receptor":[25,137],"uPAR":[26,57,115,129],"serine":[29],"protease":[30],"uPA.":[31,148],"While":[32],"preparing":[33],"derivatives":[34,90],"a":[36,43,107,139],"fragment-like":[37],"compound":[38,48],"previously":[40],"emerged":[41],"from":[42],"computational":[44],"screen,":[45],"we":[46],"identified":[47],"5":[49],"(IPR-3242),":[50],"which":[51],"inhibited":[52,104],"binding":[53,105],"uPA":[55],"to":[56,69,73,91,114,128,145,147,153,157],"with":[58],"submicromolar":[59],"IC":[60],"50":[61],"s.":[62],"The":[63],"high":[64],"inhibition":[65,162],"potency":[66],"prompted":[67],"us":[68],"carry":[70],"out":[71,75,156],"studies":[72,150],"rule":[74],"potential":[76],"aggregation,":[77],"lack":[78],"stability,":[80],"reactivity,":[81],"nonspecific":[83],"inhibition.":[84],"We":[85],"designed":[86],"prepared":[88],"16":[89],"further":[92],"explore":[93],"role":[95],"each":[97],"substituent.":[98],"Interestingly,":[99],"compounds":[101,126],"only":[102],"partially":[103],"fluorescently":[108],"labeled":[109],"\u03b1-helical":[110],"peptide":[111],"binds":[113],"at":[116,166],"uPAR\u00b7uPA":[118,133],"interface.":[119],"Collectively,":[120],"results":[122],"suggest":[123],"bind":[127,146],"outside":[130],"interface,":[134],"trapping":[135],"into":[138],"conformation":[140],"not":[143],"able":[144],"Additional":[149],"will":[151],"have":[152],"be":[154],"carried":[155],"determine":[158],"whether":[159],"this":[160],"unique":[161],"mechanism":[163],"can":[164],"occur":[165],"surface.":[169]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2020-12-21T00:00:00"}
