{"id":"https://openalex.org/W7126044546","doi":"https://doi.org/10.1002/advs.202518793","title":"Potent and Selective IGF\u2010IIR\u2010Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins","display_name":"Potent and Selective IGF\u2010IIR\u2010Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins","publication_year":2026,"publication_date":"2026-01-28","ids":{"openalex":"https://openalex.org/W7126044546","doi":"https://doi.org/10.1002/advs.202518793","pmid":"https://pubmed.ncbi.nlm.nih.gov/41605838","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13248831"},"language":"en","primary_location":{"id":"doi:10.1002/advs.202518793","doi":"https://doi.org/10.1002/advs.202518793","is_oa":true,"landing_page_url":"https://doi.org/10.1002/advs.202518793","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202518793","source":{"id":"https://openalex.org/S2737737698","display_name":"Advanced Science","issn_l":"2198-3844","issn":["2198-3844"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","jufo-1","ki-jl-2","medline","norway-1","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Advanced Science","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202518793","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100981380","display_name":"Yuan Zhao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yuan Zhao","raw_affiliation_strings":["Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056072624","display_name":"Yaxian Liao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yaxian Liao","raw_affiliation_strings":["Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068083267","display_name":"Pengyun Li","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Pengyun Li","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113300136","display_name":"Regina Stasser de Gonzalez","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Regina Stasser de Gonzalez","raw_affiliation_strings":["Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023391698","display_name":"Xuankun Chen","orcid":"https://orcid.org/0000-0001-6006-7360","observed_orcids":["https://orcid.org/0000-0001-6006-7360"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xuankun Chen","raw_affiliation_strings":["Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5018796223","display_name":"Nicholas S. Nieto","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nicholas S. Nieto","raw_affiliation_strings":["Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088670445","display_name":"Florence M. Brunel","orcid":"https://orcid.org/0000-0002-5319-0528","observed_orcids":["https://orcid.org/0000-0002-5319-0528"]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Florence M. Brunel","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070622489","display_name":"Nick Cox","orcid":"https://orcid.org/0000-0002-0374-2902","observed_orcids":["https://orcid.org/0000-0002-0374-2902","https://orcid.org/0009-0008-2413-5627"]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nick Cox","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025543241","display_name":"Joseph R. Stock","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph Stock","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124286134","display_name":"Matthew McHenry","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Matthew McHenry","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008264903","display_name":"Guangsen Fu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Guangsen Fu","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050955013","display_name":"Penghsuan Huang","orcid":"https://orcid.org/0000-0002-5058-5399","observed_orcids":["https://orcid.org/0000-0002-5058-5399"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Penghsuan Huang","raw_affiliation_strings":["Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124228049","display_name":"Wenxin Wu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wenxin Wu","raw_affiliation_strings":["Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081988308","display_name":"Deqin Cai","orcid":"https://orcid.org/0000-0002-3143-2362","observed_orcids":["https://orcid.org/0000-0002-3143-2362"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Deqin Cai","raw_affiliation_strings":["Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100746152","display_name":"Lingjun Li","orcid":"https://orcid.org/0000-0003-0056-3869","observed_orcids":["https://orcid.org/0000-0003-0056-3869"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lingjun Li","raw_affiliation_strings":["Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]},{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063759903","display_name":"Alexander N. Zaykov","orcid":"https://orcid.org/0000-0001-6908-9195","observed_orcids":["https://orcid.org/0000-0001-6908-9195"]},"institutions":[{"id":"https://openalex.org/I4210106615","display_name":"Novo Nordisk (United States)","ror":"https://ror.org/011y67d23","country_code":"US","type":"company","lineage":["https://openalex.org/I189090001","https://openalex.org/I2801134892","https://openalex.org/I4210106615","https://openalex.org/I4210159963"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Alexander N. Zaykov","raw_affiliation_strings":["Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA"],"raw_orcid":"https://orcid.org/0000-0001-6908-9195","affiliations":[{"raw_affiliation_string":"Chemical Biology Novo Nordisk US R&D  Lexington Massachusetts USA","institution_ids":["https://openalex.org/I4210106615"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5087354808","display_name":"Weiping Tang","orcid":"https://orcid.org/0000-0002-0039-3196","observed_orcids":["https://orcid.org/0000-0002-0039-3196"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Weiping Tang","raw_affiliation_strings":["Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA"],"raw_orcid":"https://orcid.org/0000-0002-0039-3196","affiliations":[{"raw_affiliation_string":"Department of Chemistry University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]},{"raw_affiliation_string":"Lachman Institute of Pharmaceutical Development School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin USA","institution_ids":["https://openalex.org/I135310074"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5063759903","https://openalex.org/A5087354808"],"corresponding_institution_ids":["https://openalex.org/I135310074","https://openalex.org/I4210106615"],"apc_list":{"value":6730,"currency":"USD","value_usd":6730},"apc_paid":{"value":6730,"currency":"USD","value_usd":6730},"fwci":8.1744,"has_fulltext":true,"cited_by_count":4,"citation_normalized_percentile":{"value":0.97358714,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":98},"biblio":{"volume":"13","issue":"30","first_page":"e18793","last_page":"e18793"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9843999743461609,"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":0.9843999743461609,"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/T10587","display_name":"Autophagy in Disease and Therapy","score":0.002099999925121665,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"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/T12477","display_name":"Toxin Mechanisms and Immunotoxins","score":0.0015999999595806003,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/lysosome-targeting-chimeras","display_name":"lysosome-targeting chimeras","score":0.9639999866485596},{"id":"https://openalex.org/keywords/bifunctional-degraders","display_name":"bifunctional degraders","score":0.8370000123977661},{"id":"https://openalex.org/keywords/lysosomal-degradation","display_name":"lysosomal degradation","score":0.902999997138977},{"id":"https://openalex.org/keywords/protein-internalization","display_name":"protein internalization","score":0.6589999794960022},{"id":"https://openalex.org/keywords/pd-l1-degradation","display_name":"PD-L1 degradation","score":0.7710000276565552},{"id":"https://openalex.org/keywords/mannose-6-phosphate-receptor","display_name":"mannose 6-phosphate receptor","score":0.8019999861717224},{"id":"https://openalex.org/keywords/igf-1-receptor","display_name":"IGF-1 receptor","score":0.6110000014305115},{"id":"https://openalex.org/keywords/insulin-receptor-isoform-a","display_name":"insulin receptor isoform A","score":0.8880000114440918},{"id":"https://openalex.org/keywords/secreted-proteins","display_name":"secreted proteins","score":0.6140000224113464},{"id":"https://openalex.org/keywords/membrane-proteins","display_name":"membrane proteins","score":0.9279999732971191},{"id":"https://openalex.org/keywords/targeted-protein-degradation","display_name":"targeted protein degradation","score":0.546999990940094}],"concepts":[{"id":"https://openalex.org/C139770010","wikidata":"https://www.wikidata.org/wiki/Q1339807","display_name":"Internalization","level":3,"score":0.875},{"id":"https://openalex.org/C2780216420","wikidata":"https://www.wikidata.org/wiki/Q83330","display_name":"Lysosome","level":3,"score":0.6699000000953674},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.578499972820282},{"id":"https://openalex.org/C28406088","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Extracellular","level":2,"score":0.5185999870300293},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.5078999996185303},{"id":"https://openalex.org/C120694314","wikidata":"https://www.wikidata.org/wiki/Q6750941","display_name":"Mannose 6-phosphate receptor","level":4,"score":0.5034000277519226},{"id":"https://openalex.org/C2780443040","wikidata":"https://www.wikidata.org/wiki/Q3737863","display_name":"Bifunctional","level":3,"score":0.47859999537467957},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.45019999146461487},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4406999945640564},{"id":"https://openalex.org/C197462201","wikidata":"https://www.wikidata.org/wiki/Q2476074","display_name":"Cell surface receptor","level":3,"score":0.4318000078201294},{"id":"https://openalex.org/C28005876","wikidata":"https://www.wikidata.org/wiki/Q189814","display_name":"Endocytosis","level":3,"score":0.41609999537467957},{"id":"https://openalex.org/C144647389","wikidata":"https://www.wikidata.org/wiki/Q423042","display_name":"Membrane protein","level":3,"score":0.40529999136924744},{"id":"https://openalex.org/C11569505","wikidata":"https://www.wikidata.org/wiki/Q727265","display_name":"Asialoglycoprotein receptor","level":4,"score":0.3749000132083893},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3564999997615814},{"id":"https://openalex.org/C2778106830","wikidata":"https://www.wikidata.org/wiki/Q29548","display_name":"Cell membrane","level":3,"score":0.32679998874664307},{"id":"https://openalex.org/C57581600","wikidata":"https://www.wikidata.org/wiki/Q2449730","display_name":"Transport protein","level":2,"score":0.3027999997138977},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.30149999260902405},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.3005000054836273},{"id":"https://openalex.org/C86756495","wikidata":"https://www.wikidata.org/wiki/Q7702931","display_name":"Ternary complex","level":3,"score":0.3001999855041504},{"id":"https://openalex.org/C2775960820","wikidata":"https://www.wikidata.org/wiki/Q408378","display_name":"Growth factor","level":3,"score":0.2808000147342682},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.2800999879837036},{"id":"https://openalex.org/C21936154","wikidata":"https://www.wikidata.org/wiki/Q14911786","display_name":"Insulin-like growth factor 2 receptor","level":5,"score":0.2678999900817871},{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.2671999931335449}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","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":"D007335","descriptor_name":"Insulin-Like Growth Factor II","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D007335","descriptor_name":"Insulin-Like Growth Factor II","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008247","descriptor_name":"Lysosomes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008565","descriptor_name":"Membrane Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D017527","descriptor_name":"Receptor, IGF Type 2","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D017527","descriptor_name":"Receptor, IGF Type 2","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true}],"locations_count":4,"locations":[{"id":"doi:10.1002/advs.202518793","doi":"https://doi.org/10.1002/advs.202518793","is_oa":true,"landing_page_url":"https://doi.org/10.1002/advs.202518793","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202518793","source":{"id":"https://openalex.org/S2737737698","display_name":"Advanced Science","issn_l":"2198-3844","issn":["2198-3844"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","jufo-1","ki-jl-2","medline","norway-1","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Advanced Science","raw_type":"journal-article"},{"id":"pmid:41605838","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41605838","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":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13248831","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13248831/pdf/ADVS-13-e18793.pdf","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Adv Sci (Weinh)","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:b5d3794ecd4142c49169c1fb55e8ca96","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/b5d3794ecd4142c49169c1fb55e8ca96","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Advanced Science, Vol 13, Iss 30, Pp n/a-n/a (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.1002/advs.202518793","doi":"https://doi.org/10.1002/advs.202518793","is_oa":true,"landing_page_url":"https://doi.org/10.1002/advs.202518793","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202518793","source":{"id":"https://openalex.org/S2737737698","display_name":"Advanced Science","issn_l":"2198-3844","issn":["2198-3844"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","jufo-1","ki-jl-2","medline","norway-1","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Advanced Science","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.5683000087738037}],"study_designs":[],"awards":[{"id":"https://openalex.org/G252022968","display_name":null,"funder_award_id":"R35GM148266","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G5013080170","display_name":null,"funder_award_id":"R01DK071801","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G5210205453","display_name":null,"funder_award_id":"S10OD025084","funder_id":"https://openalex.org/F4320337432","funder_display_name":"Center for Scientific Review"},{"id":"https://openalex.org/G6635003544","display_name":null,"funder_award_id":"NIH R35GM148266","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G7018735995","display_name":"Acquisition of a High Resolution High Speed MALDI Mass Spectrometer for Biomedical Research at UW-Madison","funder_award_id":"1s10od025084-01","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G7406245512","display_name":null,"funder_award_id":"S10OD028473","funder_id":"https://openalex.org/F4320337432","funder_display_name":"Center for Scientific Review"},{"id":"https://openalex.org/G7430799186","display_name":"Acquisition of a Dual-Source, High-Performance, Ion Mobility, Quadrupole Time-of-Flight Mass Spectrometry System for Biomedical Research at UW-Madison","funder_award_id":"1s10od028473-01a1","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G886646266","display_name":null,"funder_award_id":"R01AG052324","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G9000879955","display_name":"Mass Spectrometric Studies of Neuropeptides in Feeding","funder_award_id":"R01DK071801","funder_id":"https://openalex.org/F4320337357","funder_display_name":"National Institute of Diabetes and Digestive and Kidney Diseases"},{"id":"https://openalex.org/G9000896066","display_name":"DiLeu-enabled multiplexed quantitation for biomarker discovery and validation in Alzheimer\u2019s disease","funder_award_id":"R01AG052324","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G9000913433","display_name":"Chemical Synthesis and Biological Application of Carbohydrates and Glycoconjugates","funder_award_id":"R35GM148266","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320322436","display_name":"Novo Nordisk","ror":"https://ror.org/0435rc536"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","ror":"https://ror.org/049v75w11"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"},{"id":"https://openalex.org/F4320337357","display_name":"National Institute of Diabetes and Digestive and Kidney Diseases","ror":"https://ror.org/00adh9b73"},{"id":"https://openalex.org/F4320337432","display_name":"Center for Scientific Review","ror":"https://ror.org/04r5s4b52"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7126044546.pdf","grobid_xml":"https://content.openalex.org/works/W7126044546.grobid-xml"},"referenced_works_count":44,"referenced_works":["https://openalex.org/W12620930","https://openalex.org/W1504464280","https://openalex.org/W1537039018","https://openalex.org/W1555861554","https://openalex.org/W1976143235","https://openalex.org/W1983857866","https://openalex.org/W1990926444","https://openalex.org/W2012034410","https://openalex.org/W2017979183","https://openalex.org/W2074501368","https://openalex.org/W2074647644","https://openalex.org/W2084210525","https://openalex.org/W2093117233","https://openalex.org/W2131380785","https://openalex.org/W2136388877","https://openalex.org/W2151683271","https://openalex.org/W2283163602","https://openalex.org/W2767251210","https://openalex.org/W2890850288","https://openalex.org/W2949109587","https://openalex.org/W3045619116","https://openalex.org/W3092196597","https://openalex.org/W3133738516","https://openalex.org/W3136448722","https://openalex.org/W3153520238","https://openalex.org/W3158001674","https://openalex.org/W3161698207","https://openalex.org/W3195114088","https://openalex.org/W4205379795","https://openalex.org/W4296691508","https://openalex.org/W4309796326","https://openalex.org/W4323031792","https://openalex.org/W4387017130","https://openalex.org/W4388014235","https://openalex.org/W4388574258","https://openalex.org/W4389452850","https://openalex.org/W4393032910","https://openalex.org/W4402366130","https://openalex.org/W4402827313","https://openalex.org/W4403233863","https://openalex.org/W4404120620","https://openalex.org/W4407746084","https://openalex.org/W4413895509","https://openalex.org/W4416815614"],"related_works":["https://openalex.org/W4388014235","https://openalex.org/W4388574258","https://openalex.org/W4392189683","https://openalex.org/W7163428612","https://openalex.org/W4389462841","https://openalex.org/W4407746084","https://openalex.org/W4230707912","https://openalex.org/W4387424287","https://openalex.org/W7216600773","https://openalex.org/W4240984038"],"abstract_inverted_index":{"Lysosome":[0],"targeting":[1,29],"chimeras":[2],"(LYTACs)":[3],"represent":[4],"a":[5,23,27,33,119,161,171],"promising":[6],"strategy":[7],"to":[8,26,139],"harness":[9],"lysosomal":[10],"degradation":[11,151],"for":[12,134],"eliminating":[13],"extracellular":[14],"and":[15,39,73,82,105,128,141,150,155,175],"membrane":[16],"disease-causing":[17],"proteins.":[18,157],"These":[19],"bifunctional":[20,145],"molecules":[21],"link":[22],"target":[24],"protein":[25],"lysosome":[28],"receptor":[30,49,59,103,107],"(LTR),":[31],"forming":[32],"ternary":[34],"complex":[35,72],"that":[36],"drives":[37],"internalization":[38,149],"degradation.":[40,190],"The":[41,143,182],"first":[42],"generation":[43],"of":[44,152],"LYTAC":[45,165],"used":[46],"cation-independent":[47],"mannose-6-phosphate":[48],"(CI-M6PR),":[50],"also":[51],"known":[52],"as":[53,61,67,89],"Type":[54,98],"II":[55],"insulin-like":[56,100],"growth":[57,101],"factor":[58,102],"(IGF-IIR),":[60],"the":[62,68],"LTR,":[63],"with":[64,124],"polymeric":[65],"glycopeptides":[66],"ligands.":[69],"However,":[70,93],"their":[71],"heterogeneous":[74],"composition":[75],"limits":[76],"therapeutic":[77],"potential.":[78],"To":[79],"improve":[80],"specificity":[81],"efficacy,":[83],"natural":[84],"IGF-II":[85,95,121],"has":[86],"been":[87],"explored":[88],"an":[90],"alternative":[91],"ligand.":[92],"wild-type":[94],"activates":[96],"both":[97,153],"I":[99],"(IGF-IR)":[104],"insulin":[106],"isoform":[108],"A":[109],"(IR-A),":[110],"posing":[111],"off-target":[112],"risks.":[113],"In":[114],"this":[115],"study,":[116],"we":[117,159],"engineered":[118],"novel":[120],"mutant":[122],"(mutIGF-II)":[123],"two":[125],"mutations":[126],"(Del1-7":[127],"Y27L),":[129],"which":[130],"confer":[131],"high":[132],"affinity":[133],"IGF-IIR":[135],"while":[136],"minimizing":[137],"binding":[138],"IGF-IR":[140],"IR-A.":[142],"mutIGF-II-based":[144,184],"degraders":[146],"significantly":[147],"enhanced":[148],"secreted":[154,183],"membrane-bound":[156],"Additionally,":[158],"developed":[160],"practical":[162],"all-protein":[163],"mutIGF-II":[164,169],"by":[166],"genetically":[167],"encoding":[168],"into":[170,178],"mammalian":[172],"expression":[173],"vector":[174],"transfecting":[176],"it":[177],"cancer-relevant":[179],"cell":[180],"lines.":[181],"PD-L1":[185,189],"degrader":[186],"effectively":[187],"induced":[188]},"counts_by_year":[{"year":2026,"cited_by_count":4}],"updated_date":"2026-11-01T11:40:01.658920","created_date":"2026-01-30T00:00:00"}