{"id":"https://openalex.org/W7212944857","doi":"https://doi.org/10.64898/2026.09.10.750156","title":"A Proximity-Driven Functional Screening Platform for the Discovery of Noninhibitory USP7 Ligand Enabling Targeted Protein Stabilization","display_name":"A Proximity-Driven Functional Screening Platform for the Discovery of Noninhibitory USP7 Ligand Enabling Targeted Protein Stabilization","publication_year":2026,"publication_date":"2026-09-14","ids":{"openalex":"https://openalex.org/W7212944857","doi":"https://doi.org/10.64898/2026.09.10.750156"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.10.750156","doi":"https://doi.org/10.64898/2026.09.10.750156","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.10.750156","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/14/2026.09.10.750156.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/14/2026.09.10.750156.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5151634196","display_name":"Kate E Young","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I70983195","display_name":"Syracuse University","ror":"https://ror.org/025r5qe02","country_code":"US","type":"education","lineage":["https://openalex.org/I70983195"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kate E. Young","raw_affiliation_strings":["Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244","institution_ids":["https://openalex.org/I70983195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5120384650","display_name":"Janitha Kumarathunga","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I70983195","display_name":"Syracuse University","ror":"https://ror.org/025r5qe02","country_code":"US","type":"education","lineage":["https://openalex.org/I70983195"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Janitha Kumarathunga","raw_affiliation_strings":["Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244","institution_ids":["https://openalex.org/I70983195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5151670600","display_name":"Hiruni Kandambi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I70983195","display_name":"Syracuse University","ror":"https://ror.org/025r5qe02","country_code":"US","type":"education","lineage":["https://openalex.org/I70983195"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hiruni Kandambi","raw_affiliation_strings":["Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244","institution_ids":["https://openalex.org/I70983195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5151647560","display_name":"Vitoria Fernandes Ferro","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I70983195","display_name":"Syracuse University","ror":"https://ror.org/025r5qe02","country_code":"US","type":"education","lineage":["https://openalex.org/I70983195"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vitoria Fernandes Ferro","raw_affiliation_strings":["Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244","institution_ids":["https://openalex.org/I70983195"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5061643726","display_name":"Weijun Gui","orcid":"https://orcid.org/0000-0001-5936-8262","observed_orcids":["https://orcid.org/0000-0001-5936-8262"]},"institutions":[{"id":"https://openalex.org/I70983195","display_name":"Syracuse University","ror":"https://ror.org/025r5qe02","country_code":"US","type":"education","lineage":["https://openalex.org/I70983195"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Weijun Gui","raw_affiliation_strings":["Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Syracuse University, 111 College Place. CST 1-133, Syracuse, NY 13244","institution_ids":["https://openalex.org/I70983195"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5061643726"],"corresponding_institution_ids":["https://openalex.org/I70983195"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.5292999744415283,"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"}},"topics":[{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.5292999744415283,"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/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.46309998631477356,"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/T10911","display_name":"Chemical Synthesis and Analysis","score":0.003100000089034438,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/usp7","display_name":"USP7","score":0.8009999990463257},{"id":"https://openalex.org/keywords/proteasomal-degradation","display_name":"proteasomal degradation","score":0.7630000114440918}],"concepts":[{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.6003999710083008},{"id":"https://openalex.org/C102658986","wikidata":"https://www.wikidata.org/wiki/Q5266092","display_name":"Deubiquitinating enzyme","level":4,"score":0.5630000233650208},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.4909000098705292},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4880000054836273},{"id":"https://openalex.org/C2986374874","wikidata":"https://www.wikidata.org/wiki/Q8054","display_name":"Protein function","level":3,"score":0.48339998722076416},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.46140000224113464},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.45879998803138733},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.430400013923645},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4251999855041504},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4065999984741211},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4036000072956085},{"id":"https://openalex.org/C2780443040","wikidata":"https://www.wikidata.org/wiki/Q3737863","display_name":"Bifunctional","level":3,"score":0.33410000801086426},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.3327000141143799},{"id":"https://openalex.org/C2908868211","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin-Protein Ligases","level":5,"score":0.3312000036239624},{"id":"https://openalex.org/C109095088","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Protein ligand","level":2,"score":0.32910001277923584},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.32820001244544983},{"id":"https://openalex.org/C2780430158","wikidata":"https://www.wikidata.org/wiki/Q7685902","display_name":"Target protein","level":3,"score":0.32100000977516174},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.31529998779296875},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.3109999895095825},{"id":"https://openalex.org/C10679952","wikidata":"https://www.wikidata.org/wiki/Q5308937","display_name":"Druggability","level":3,"score":0.30570000410079956},{"id":"https://openalex.org/C2988375501","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein stability","level":2,"score":0.30239999294281006},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.28630000352859497},{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.272599995136261},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.2718000113964081},{"id":"https://openalex.org/C27740335","wikidata":"https://www.wikidata.org/wiki/Q14878333","display_name":"Proteasome","level":2,"score":0.2711000144481659},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.27070000767707825},{"id":"https://openalex.org/C171897839","wikidata":"https://www.wikidata.org/wiki/Q417841","display_name":"Protein family","level":3,"score":0.25760000944137573},{"id":"https://openalex.org/C2777066959","wikidata":"https://www.wikidata.org/wiki/Q869711","display_name":"Cricetulus","level":4,"score":0.25209999084472656},{"id":"https://openalex.org/C2994592520","wikidata":"https://www.wikidata.org/wiki/Q5090496","display_name":"Substrate specificity","level":3,"score":0.25209999084472656},{"id":"https://openalex.org/C171852809","wikidata":"https://www.wikidata.org/wiki/Q731154","display_name":"Chemical biology","level":2,"score":0.25200000405311584}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.10.750156","doi":"https://doi.org/10.64898/2026.09.10.750156","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.10.750156","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/14/2026.09.10.750156.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.10.750156","doi":"https://doi.org/10.64898/2026.09.10.750156","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.10.750156","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/14/2026.09.10.750156.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.5683000087738037}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320309532","display_name":"Syracuse University","ror":"https://ror.org/025r5qe02"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7212944857.pdf","grobid_xml":"https://content.openalex.org/works/W7212944857.grobid-xml"},"referenced_works_count":46,"referenced_works":["https://openalex.org/W1968652549","https://openalex.org/W2003493907","https://openalex.org/W2015357935","https://openalex.org/W2024846074","https://openalex.org/W2032610349","https://openalex.org/W2039688006","https://openalex.org/W2070543174","https://openalex.org/W2150925238","https://openalex.org/W2151683271","https://openalex.org/W2162262059","https://openalex.org/W2289887068","https://openalex.org/W2531669199","https://openalex.org/W2756034579","https://openalex.org/W2772653075","https://openalex.org/W2789732912","https://openalex.org/W2895902705","https://openalex.org/W2914005285","https://openalex.org/W3045619116","https://openalex.org/W3120313360","https://openalex.org/W4205379795","https://openalex.org/W4210757594","https://openalex.org/W4225364558","https://openalex.org/W4283836349","https://openalex.org/W4320480893","https://openalex.org/W4322772375","https://openalex.org/W4382931451","https://openalex.org/W4384282319","https://openalex.org/W4384925180","https://openalex.org/W4385295851","https://openalex.org/W4394691816","https://openalex.org/W4396230754","https://openalex.org/W4401391081","https://openalex.org/W4401634294","https://openalex.org/W4403092008","https://openalex.org/W4408848656","https://openalex.org/W4409348674","https://openalex.org/W4409593536","https://openalex.org/W4411906243","https://openalex.org/W4412589398","https://openalex.org/W4413019576","https://openalex.org/W4413397678","https://openalex.org/W4414408776","https://openalex.org/W4415773287","https://openalex.org/W4416305383","https://openalex.org/W4416426818","https://openalex.org/W7160316512"],"related_works":["https://openalex.org/W4409593536","https://openalex.org/W4394691816","https://openalex.org/W7202253468","https://openalex.org/W4225364558","https://openalex.org/W7160316512","https://openalex.org/W4224294630","https://openalex.org/W7204449506","https://openalex.org/W7160436462","https://openalex.org/W4408848656","https://openalex.org/W4214809923"],"abstract_inverted_index":{"Abstract":[0],"Targeted":[1],"protein":[2,118,138],"stabilization":[3,139],"by":[4,102],"deubiquitinase-targeting":[5],"chimeras":[6],"(DUBTACs)":[7],"has":[8],"emerged":[9],"as":[10],"a":[11,72,91,108],"promising":[12],"therapeutic":[13],"strategy":[14],"for":[15,46,79,96,128],"preserving":[16],"the":[17,50,80,123,134],"function":[18],"of":[19,52,82,125,136],"essential":[20],"proteins.":[21],"DUBTACs":[22,47,101],"are":[23,66],"bifunctional":[24],"molecules":[25],"that":[26,54],"recruit":[27],"deubiquitinating":[28],"enzymes":[29],"(DUBs)":[30],"to":[31,107],"remove":[32],"ubiquitin":[33],"chains":[34],"from":[35],"substrate":[36],"proteins,":[37],"thereby":[38],"preventing":[39],"their":[40,59],"proteasomal":[41],"degradation.":[42],"A":[43],"key":[44],"requirement":[45],"development":[48,135],"is":[49],"identification":[51],"ligands":[53,65],"bind":[55],"DUBs":[56],"without":[57],"impairing":[58],"catalytic":[60],"activity.":[61],"However,":[62],"such":[63],"noninhibitory":[64,83,94],"exceedingly":[67],"rare.":[68],"Here,":[69],"we":[70,89,99],"report":[71],"novel":[73],"proximity-driven":[74],"on-bead":[75],"functional":[76],"screening":[77],"platform":[78,127],"discovery":[81],"DUB":[84,130],"ligands.":[85],"Using":[86],"this":[87,104,126],"approach,":[88],"discovered":[90],"previously":[92],"unreported":[93],"ligand":[95,106],"USP7.":[97],"Furthermore,":[98],"generated":[100],"conjugating":[103],"USP7":[105],"CFTR-binding":[109],"ligand.":[110],"Our":[111],"lead":[112],"compound,":[113],"WJ045,":[114],"effectively":[115],"stabilized":[116],"CFTR":[117],"levels":[119],"in":[120],"cells,":[121],"demonstrating":[122],"potential":[124],"discovering":[129],"recruiters":[131],"and":[132],"facilitating":[133],"targeted":[137],"therapeutics.":[140]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-09-15T00:00:00"}