{"id":"https://openalex.org/W7162850588","doi":"https://doi.org/10.1021/acs.jcim.6c00470","title":"Binding Mechanism of UAMC-1110 to Fibroblast Activation Protein","display_name":"Binding Mechanism of UAMC-1110 to Fibroblast Activation Protein","publication_year":2026,"publication_date":"2026-05-30","ids":{"openalex":"https://openalex.org/W7162850588","doi":"https://doi.org/10.1021/acs.jcim.6c00470","pmid":"https://pubmed.ncbi.nlm.nih.gov/42217238"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.6c00470","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00470","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5137455461","display_name":"Joep W. Wals","orcid":"https://orcid.org/0000-0002-6439-0453"},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Joep W. Wals","raw_affiliation_strings":["Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium"],"raw_orcid":"https://orcid.org/0000-0002-6439-0453","affiliations":[{"raw_affiliation_string":"Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium","institution_ids":["https://openalex.org/I149213910"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5135235668","display_name":"Rui P.P. Neves","orcid":"https://orcid.org/0000-0003-2032-9308"},"institutions":[{"id":"https://openalex.org/I182534213","display_name":"Universidade do Porto","ror":"https://ror.org/043pwc612","country_code":"PT","type":"education","lineage":["https://openalex.org/I182534213"]},{"id":"https://openalex.org/I4210138594","display_name":"Rede de Qu\u00edmica e Tecnologia","ror":"https://ror.org/04j14t006","country_code":"PT","type":"nonprofit","lineage":["https://openalex.org/I4210138594"]}],"countries":["PT"],"is_corresponding":false,"raw_author_name":"Rui P. P. Neves","raw_affiliation_strings":["LAQV@REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal"],"raw_orcid":"https://orcid.org/0000-0003-2032-9308","affiliations":[{"raw_affiliation_string":"LAQV@REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal","institution_ids":["https://openalex.org/I182534213","https://openalex.org/I4210138594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5126315445","display_name":"Pedro A. Fernandes","orcid":null},"institutions":[{"id":"https://openalex.org/I182534213","display_name":"Universidade do Porto","ror":"https://ror.org/043pwc612","country_code":"PT","type":"education","lineage":["https://openalex.org/I182534213"]},{"id":"https://openalex.org/I4210138594","display_name":"Rede de Qu\u00edmica e Tecnologia","ror":"https://ror.org/04j14t006","country_code":"PT","type":"nonprofit","lineage":["https://openalex.org/I4210138594"]}],"countries":["PT"],"is_corresponding":false,"raw_author_name":"Pedro A. Fernandes","raw_affiliation_strings":["LAQV@REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal"],"raw_orcid":"https://orcid.org/0000-0003-2748-4722","affiliations":[{"raw_affiliation_string":"LAQV@REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal","institution_ids":["https://openalex.org/I182534213","https://openalex.org/I4210138594"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5109154761","display_name":"H. Winter","orcid":null},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":true,"raw_author_name":"Hans De Winter","raw_affiliation_strings":["Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium"],"raw_orcid":"https://orcid.org/0000-0002-4450-7677","affiliations":[{"raw_affiliation_string":"Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium","institution_ids":["https://openalex.org/I149213910"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5109154761"],"corresponding_institution_ids":["https://openalex.org/I149213910"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.62061388,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"66","issue":"12","first_page":"7179","last_page":"7189"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12505","display_name":"Peptidase Inhibition and Analysis","score":0.8826000094413757,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T12505","display_name":"Peptidase Inhibition and Analysis","score":0.8826000094413757,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.011900000274181366,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"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/T11310","display_name":"Connective tissue disorders research","score":0.010499999858438969,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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"}}],"keywords":[{"id":"https://openalex.org/keywords/mechanism","display_name":"Mechanism (biology)","score":0.5626000165939331},{"id":"https://openalex.org/keywords/fibroblast","display_name":"Fibroblast","score":0.5509999990463257},{"id":"https://openalex.org/keywords/fibroblast-activation-protein-alpha","display_name":"Fibroblast activation protein, alpha","score":0.4690999984741211},{"id":"https://openalex.org/keywords/plasma-protein-binding","display_name":"Plasma protein binding","score":0.3693999946117401},{"id":"https://openalex.org/keywords/protein\u2013protein-interaction","display_name":"Protein\u2013protein interaction","score":0.3481000065803528},{"id":"https://openalex.org/keywords/binding-protein","display_name":"Binding protein","score":0.3027999997138977}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7440999746322632},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5766000151634216},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.5626000165939331},{"id":"https://openalex.org/C2780381497","wikidata":"https://www.wikidata.org/wiki/Q463418","display_name":"Fibroblast","level":3,"score":0.5509999990463257},{"id":"https://openalex.org/C111798993","wikidata":"https://www.wikidata.org/wiki/Q21117471","display_name":"Fibroblast activation protein, alpha","level":3,"score":0.4690999984741211},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.37229999899864197},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.3693999946117401},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.3481000065803528},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3142000138759613},{"id":"https://openalex.org/C553089730","wikidata":"https://www.wikidata.org/wiki/Q4914021","display_name":"Binding protein","level":3,"score":0.3027999997138977},{"id":"https://openalex.org/C125209161","wikidata":"https://www.wikidata.org/wiki/Q422816","display_name":"Enzyme activator","level":3,"score":0.29179999232292175},{"id":"https://openalex.org/C94966510","wikidata":"https://www.wikidata.org/wiki/Q2252764","display_name":"DNA-binding protein","level":4,"score":0.28049999475479126},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.28049999475479126},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2700999975204468},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.2587999999523163},{"id":"https://openalex.org/C191709040","wikidata":"https://www.wikidata.org/wiki/Q14889334","display_name":"FGF1","level":5,"score":0.25529998540878296}],"mesh":[{"descriptor_ui":"D000099167","descriptor_name":"Fibroblast Activation Protein Alpha","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008565","descriptor_name":"Membrane Proteins","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D008565","descriptor_name":"Membrane Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008565","descriptor_name":"Membrane Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D010450","descriptor_name":"Endopeptidases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012697","descriptor_name":"Serine Endopeptidases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D012697","descriptor_name":"Serine Endopeptidases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D018093","descriptor_name":"Gelatinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D018093","descriptor_name":"Gelatinases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.6c00470","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6c00470","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:42217238","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42217238","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,"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":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G1129713410","display_name":"Rational engineering of bacterial sulfur oxidoreductases for the capture and recycling of sulfur-based pollutants","funder_award_id":"2021.00391.CEECIND/CP1662/CT0003","funder_id":"https://openalex.org/F4320334779","funder_display_name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia"},{"id":"https://openalex.org/G5837344382","display_name":null,"funder_award_id":"V427319N","funder_id":"https://openalex.org/F4320321730","funder_display_name":"Fonds Wetenschappelijk Onderzoek"},{"id":"https://openalex.org/G7096498710","display_name":null,"funder_award_id":"UID/50006/2025 10.54499/UID/50006/2025","funder_id":"https://openalex.org/F4320334779","funder_display_name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia"}],"funders":[{"id":"https://openalex.org/F4320321730","display_name":"Fonds Wetenschappelijk Onderzoek","ror":"https://ror.org/03qtxy027"},{"id":"https://openalex.org/F4320334779","display_name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","ror":"https://ror.org/00snfqn58"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":46,"referenced_works":["https://openalex.org/W1976499671","https://openalex.org/W1979313952","https://openalex.org/W1980724829","https://openalex.org/W1994793426","https://openalex.org/W2002964590","https://openalex.org/W2029667189","https://openalex.org/W2030370730","https://openalex.org/W2047280630","https://openalex.org/W2047730645","https://openalex.org/W2047764904","https://openalex.org/W2058363175","https://openalex.org/W2089553497","https://openalex.org/W2092157292","https://openalex.org/W2094642658","https://openalex.org/W2097546936","https://openalex.org/W2101545809","https://openalex.org/W2110750568","https://openalex.org/W2143981217","https://openalex.org/W2147993766","https://openalex.org/W2148284063","https://openalex.org/W2168240189","https://openalex.org/W2327581403","https://openalex.org/W2330799739","https://openalex.org/W2404280981","https://openalex.org/W2467822028","https://openalex.org/W2765322245","https://openalex.org/W2792058791","https://openalex.org/W2889785065","https://openalex.org/W2891469241","https://openalex.org/W2912973389","https://openalex.org/W2921110418","https://openalex.org/W3000643563","https://openalex.org/W3009264613","https://openalex.org/W3091864100","https://openalex.org/W3192665011","https://openalex.org/W4210604819","https://openalex.org/W4224234572","https://openalex.org/W4293793251","https://openalex.org/W4306936773","https://openalex.org/W4319657197","https://openalex.org/W4320735827","https://openalex.org/W4379966959","https://openalex.org/W4382344070","https://openalex.org/W4415159754","https://openalex.org/W4415597069","https://openalex.org/W7115938862"],"related_works":[],"abstract_inverted_index":{"Fibroblast":[0],"activation":[1],"protein":[2],"(FAP)":[3],"is":[4,48,144],"an":[5],"enzyme":[6],"highly":[7],"expressed":[8],"in":[9,214],"cancer-associated":[10],"fibroblasts.":[11],"Over":[12],"the":[13,66,86,95,105,112,137,178,204,217,223,232],"past":[14],"years,":[15],"several":[16],"FAP":[17],"inhibitors":[18],"(FAPIs)":[19],"have":[20],"been":[21],"developed":[22],"for":[23,236],"tumor":[24,44],"imaging.":[25],"These":[26],"approaches":[27],"typically":[28],"involve":[29],"covalently":[30],"linking":[31],"a":[32,36,81,108,115,129,184],"metal-loaded":[33],"chelator":[34],"to":[35,50,64,93,125,216],"small":[37],"molecule":[38],"ligand":[39],"that":[40,104,118,172,210],"targets":[41],"FAP.":[42],"Prolonged":[43],"retention":[45],"of":[46,69,85,99,134,203,222],"FAPIs":[47],"desirable":[49],"support":[51],"theranostic":[52],"applications,":[53],"which":[54],"integrate":[55],"both":[56],"diagnostic":[57],"and":[58,159,187,198,227],"therapeutic":[59],"functions.":[60],"Therefore,":[61],"we":[62],"sought":[63],"elucidate":[65],"binding":[67,83,97],"mechanism":[68,98,235],"our":[70],"in-house-designed":[71],"FAPI":[72],"lead":[73],"compound,":[74],"UAMC-1110.":[75,100],"Initial":[76],"molecular":[77],"dynamics":[78],"simulations":[79,170],"yielded":[80],"noncovalent":[82],"pose":[84],"ligand.":[87],"Subsequently,":[88],"QM/MM":[89],"calculations":[90],"were":[91],"performed":[92],"investigate":[94],"covalent":[96,109,218],"Our":[101],"results":[102],"corroborate":[103],"compound":[106],"forms":[107],"complex":[110,225,237],"with":[111,120,177],"receptor":[113],"through":[114,155],"reaction":[116,224],"pathway":[117,191],"begins":[119],"proton":[121],"transfer":[122],"from":[123],"S624":[124,135],"H734,":[126,193],"followed":[127,165],"by":[128,153,163,166,196],"concerted,":[130],"asynchronous":[131],"nucleophilic":[132],"attack":[133],"on":[136],"nitrile":[138],"warhead.":[139],"The":[140],"resulting":[141],"imidate":[142,179],"anion":[143,180],"stabilized":[145],"via":[146,192],"two":[147,156],"possible":[148],"routes:":[149],"(1)":[150],"protonation":[151,162,190],"mediated":[152],"H734":[154,173],"water":[157],"molecules,":[158],"(2)":[160],"direct":[161],"Y541":[164],"reprotonation.":[167],"Covalent":[168],"MD":[169],"reveal":[171],"interacts":[174],"more":[175],"frequently":[176],"than":[181],"Y541,":[182],"identifying":[183],"previously":[185],"unrecognized":[186],"kinetically":[188],"favored":[189],"further":[194],"supported":[195],"water-density":[197],"Gibbs":[199],"energy":[200],"calculations.":[201],"Simulations":[202],"final":[205],"product":[206],"state":[207],"additionally":[208],"indicate":[209],"neither":[211],"residue":[212],"remains":[213],"proximity":[215],"adduct,":[219],"making":[220],"reversibility":[221],"unlikely":[226],"instead":[228],"suggesting":[229],"hydrolysis":[230],"as":[231],"most":[233],"plausible":[234],"dissociation.":[238]},"counts_by_year":[],"updated_date":"2026-07-22T07:51:19.307946","created_date":"2026-05-31T00:00:00"}
