{"id":"https://openalex.org/W7155608488","doi":"https://doi.org/10.64898/2026.04.22.720177","title":"DCN1 inhibitor induces fetal hemoglobin through self-limited regulation of CUL3 neddylation","display_name":"DCN1 inhibitor induces fetal hemoglobin through self-limited regulation of CUL3 neddylation","publication_year":2026,"publication_date":"2026-04-24","ids":{"openalex":"https://openalex.org/W7155608488","doi":"https://doi.org/10.64898/2026.04.22.720177"},"language":"en","primary_location":{"id":"doi:10.64898/2026.04.22.720177","doi":"https://doi.org/10.64898/2026.04.22.720177","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.04.22.720177","pdf_url":null,"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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.04.22.720177","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5052712841","display_name":"Samuel A. Miller","orcid":"https://orcid.org/0000-0002-0106-663X","observed_orcids":["https://orcid.org/0000-0002-0106-663X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Samuel A. Miller","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006107316","display_name":"Anthony Monti","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Anthony Monti","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110265846","display_name":"Enhua H. Zhou","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Enhua H. Zhou","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061115918","display_name":"Chi Hua Sarah Lin","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chi Hua Sarah Lin","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081887929","display_name":"Orna Lynch","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Orna Lynch","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045697589","display_name":"Sayani Mukherjee","orcid":"https://orcid.org/0000-0003-1914-7371","observed_orcids":["https://orcid.org/0000-0003-1914-7371"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sayani Mukherjee","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5120587904","display_name":"Cassie Hei","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Cassie Hei","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5117205298","display_name":"Robert Nicewonger","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robert Nicewonger","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063540888","display_name":"Colin Diner","orcid":"https://orcid.org/0000-0001-5883-0961","observed_orcids":["https://orcid.org/0000-0001-5883-0961"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Colin Diner","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052971123","display_name":"Alejandra Macias-Garcia","orcid":"https://orcid.org/0000-0001-8904-8761","observed_orcids":["https://orcid.org/0000-0001-8904-8761"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alejandra Macias-Garcia","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077100623","display_name":"Kristen A. Marino","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kristen Marino","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159833966","display_name":"Na Li","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Na Li","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040205341","display_name":"Ravi K. Ujjinamatada","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ravi Ujjinamatada","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5033218792","display_name":"Akshay Salegaonkar","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Akshay Salegaonkar","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029676989","display_name":"Sunil Kuppasani","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sunil Kuppasani","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083724177","display_name":"Maximilian Rogers-Grazado","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Max Rogers-Grazado","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006697675","display_name":"Corey E. Hayford","orcid":"https://orcid.org/0000-0002-3006-4852","observed_orcids":["https://orcid.org/0000-0002-3006-4852"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Corey Hayford","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5041016509","display_name":"Frank Lovering","orcid":"https://orcid.org/0000-0002-9515-8200","observed_orcids":["https://orcid.org/0000-0002-9515-8200"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Frank Lovering","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159784141","display_name":"Qing Tang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Qing Tang","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5134612479","display_name":"Yihua Ye","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yihua E. Ye","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159772221","display_name":"Wei Zhang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Wei Zhang","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049916767","display_name":"Timothy Fulton","orcid":"https://orcid.org/0000-0002-0386-1821","observed_orcids":["https://orcid.org/0000-0002-0386-1821"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Timothy Fulton","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5104348898","display_name":"Jennifer J. O'Brien","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jennifer J. O\u2019Brien","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5134598764","display_name":"Xiaoji Sun","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Xiaoji Sun","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009025844","display_name":"Atli Thorarensen","orcid":"https://orcid.org/0000-0002-6791-5809","observed_orcids":["https://orcid.org/0000-0002-6791-5809"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Atli Thorarensen","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102310960","display_name":"Mauricio Cortes","orcid":"https://orcid.org/0009-0003-6887-4011","observed_orcids":["https://orcid.org/0009-0003-6887-4011"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mauricio Cortes","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5084389353","display_name":"Cameron C. Trenor","orcid":"https://orcid.org/0000-0003-3954-7882","observed_orcids":["https://orcid.org/0000-0003-3954-7882"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Cameron C. Trenor","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5107850061","display_name":"Sriram Krishnamoorthy","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Sriram Krishnamoorthy","raw_affiliation_strings":["Cellarity Inc; Somerville, MA 02141 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cellarity Inc; Somerville, MA 02141 USA","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5107850061"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"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/T10554","display_name":"Hemoglobinopathies and Related Disorders","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"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/T10554","display_name":"Hemoglobinopathies and Related Disorders","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"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/T12094","display_name":"Hemoglobin structure and function","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell 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/T13426","display_name":"Kruppel-like factors research","score":9.999999747378752e-05,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/fetal-hemoglobin","display_name":"fetal hemoglobin","score":0.9070000052452087},{"id":"https://openalex.org/keywords/globin-switching","display_name":"globin switching","score":0.7480000257492065},{"id":"https://openalex.org/keywords/beta-hemoglobinopathies","display_name":"\u03b2-hemoglobinopathies","score":0.8830000162124634},{"id":"https://openalex.org/keywords/sickle-cell-disease","display_name":"sickle cell disease","score":0.9990000128746033},{"id":"https://openalex.org/keywords/beta-thalassemia","display_name":"beta-thalassemia","score":0.9869999885559082},{"id":"https://openalex.org/keywords/covalent-inhibitors","display_name":"covalent inhibitors","score":0.6370000243186951},{"id":"https://openalex.org/keywords/histone-demethylation","display_name":"histone demethylation","score":0.9200000166893005},{"id":"https://openalex.org/keywords/chromatin-regulation","display_name":"chromatin regulation","score":0.7580000162124634},{"id":"https://openalex.org/keywords/single-cell-transcriptomics","display_name":"single-cell transcriptomics","score":0.7570000290870667}],"concepts":[{"id":"https://openalex.org/C45005369","wikidata":"https://www.wikidata.org/wiki/Q21115705","display_name":"Neddylation","level":5,"score":0.7347999811172485},{"id":"https://openalex.org/C2776317666","wikidata":"https://www.wikidata.org/wiki/Q2496436","display_name":"Fetal hemoglobin","level":4,"score":0.728600025177002},{"id":"https://openalex.org/C2778567606","wikidata":"https://www.wikidata.org/wiki/Q41797435","display_name":"Cullin","level":5,"score":0.7171000242233276},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.517300009727478},{"id":"https://openalex.org/C41091548","wikidata":"https://www.wikidata.org/wiki/Q26939","display_name":"Epigenetics","level":3,"score":0.4749999940395355},{"id":"https://openalex.org/C134459356","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin ligase","level":4,"score":0.42730000615119934},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.41280001401901245},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.40130001306533813},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.400299996137619},{"id":"https://openalex.org/C2779231659","wikidata":"https://www.wikidata.org/wiki/Q6953444","display_name":"NEDD8","level":5,"score":0.38609999418258667},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3700000047683716},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.35260000824928284},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.34470000863075256},{"id":"https://openalex.org/C171122931","wikidata":"https://www.wikidata.org/wiki/Q6324626","display_name":"K562 cells","level":3,"score":0.34139999747276306},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.3402999937534332},{"id":"https://openalex.org/C2776515853","wikidata":"https://www.wikidata.org/wiki/Q2191895","display_name":"Iodoacetamide","level":4,"score":0.30230000615119934},{"id":"https://openalex.org/C2780225316","wikidata":"https://www.wikidata.org/wiki/Q7131441","display_name":"Panobinostat","level":5,"score":0.2948000133037567},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.29420000314712524},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.2752000093460083},{"id":"https://openalex.org/C125996951","wikidata":"https://www.wikidata.org/wiki/Q412234","display_name":"Globin","level":3,"score":0.27489998936653137},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.2685000002384186},{"id":"https://openalex.org/C2776262904","wikidata":"https://www.wikidata.org/wiki/Q905901","display_name":"Vorinostat","level":5,"score":0.26759999990463257},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.26159998774528503},{"id":"https://openalex.org/C2776156784","wikidata":"https://www.wikidata.org/wiki/Q3491954","display_name":"Humanized mouse","level":3,"score":0.26159998774528503},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.2572999894618988}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.04.22.720177","doi":"https://doi.org/10.64898/2026.04.22.720177","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.04.22.720177","pdf_url":null,"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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.04.22.720177","doi":"https://doi.org/10.64898/2026.04.22.720177","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.04.22.720177","pdf_url":null,"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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9922999739646912,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":70,"referenced_works":["https://openalex.org/W1584253018","https://openalex.org/W1771805953","https://openalex.org/W1964909962","https://openalex.org/W1973062929","https://openalex.org/W1974742081","https://openalex.org/W1977076243","https://openalex.org/W1990738826","https://openalex.org/W1991631628","https://openalex.org/W1992274074","https://openalex.org/W2008989169","https://openalex.org/W2011527976","https://openalex.org/W2026939327","https://openalex.org/W2033275964","https://openalex.org/W2054523011","https://openalex.org/W2076194625","https://openalex.org/W2081794370","https://openalex.org/W2083334037","https://openalex.org/W2086851301","https://openalex.org/W2102619694","https://openalex.org/W2134703818","https://openalex.org/W2141340108","https://openalex.org/W2155090266","https://openalex.org/W2157982286","https://openalex.org/W2168395641","https://openalex.org/W2170551349","https://openalex.org/W2171808845","https://openalex.org/W2274632826","https://openalex.org/W2313541759","https://openalex.org/W2334263927","https://openalex.org/W2339933044","https://openalex.org/W2341539131","https://openalex.org/W2592339311","https://openalex.org/W2610475181","https://openalex.org/W2741508285","https://openalex.org/W2755709827","https://openalex.org/W2765683432","https://openalex.org/W2790047152","https://openalex.org/W2800392236","https://openalex.org/W2802276608","https://openalex.org/W2887206273","https://openalex.org/W2888972707","https://openalex.org/W2907927681","https://openalex.org/W2909812732","https://openalex.org/W2914871918","https://openalex.org/W2925075625","https://openalex.org/W2946672260","https://openalex.org/W2953622121","https://openalex.org/W2960979937","https://openalex.org/W3003441605","https://openalex.org/W3046950215","https://openalex.org/W3091936764","https://openalex.org/W3108594068","https://openalex.org/W3138662427","https://openalex.org/W3162029322","https://openalex.org/W3164659906","https://openalex.org/W3165253641","https://openalex.org/W3192398634","https://openalex.org/W4211089719","https://openalex.org/W4230707000","https://openalex.org/W4281550335","https://openalex.org/W4380986318","https://openalex.org/W4396674479","https://openalex.org/W4396789222","https://openalex.org/W4399250968","https://openalex.org/W4400314240","https://openalex.org/W4400314304","https://openalex.org/W4401364677","https://openalex.org/W4401554310","https://openalex.org/W4404473819","https://openalex.org/W4409086474"],"related_works":["https://openalex.org/W4417015374","https://openalex.org/W2582223232","https://openalex.org/W7221075695","https://openalex.org/W2563600223","https://openalex.org/W2593225494","https://openalex.org/W2980086736","https://openalex.org/W1992681592","https://openalex.org/W3037821580","https://openalex.org/W2979794493","https://openalex.org/W2560828886"],"abstract_inverted_index":{"ABSTRACT":[0],"Few":[1],"genetic":[2,80],"loci":[3],"are":[4],"as":[5,7,196],"well-characterized":[6],"the":[8,13,93,169,213,227],"globin":[9,50,126,139],"gene":[10],"locus,":[11],"and":[12,37,49,73,82,125,141,146,154,171,198,226,250,256],"substitution":[14],"of":[15,90,95,101,103,129,132,157,173,207,215,229,247],"healthy":[16,254],"\u03b3-globin":[17],"(HbF)":[18],"for":[19,30,262,271],"missing":[20],"or":[21,65,159],"mutated":[22],"\u03b2-globin":[23],"(HbB)":[24],"is":[25,260,267],"an":[26,87,238],"established":[27],"therapeutic":[28,54,224],"strategy":[29],"\u03b2-hemoglobinopathies":[31],"including":[32],"sickle":[33],"cell":[34],"disease":[35],"(SCD)":[36],"\u03b2-thalassemia.":[38],"Although":[39],"substantial":[40],"progress":[41],"has":[42],"been":[43],"made":[44],"in":[45,92,111,144,147,194,199,253],"understanding":[46],"HbF":[47,60,133,142,195,251],"derepression":[48],"switching,":[51],"many":[52],"current":[53,205],"strategies":[55],"involving":[56],"small":[57],"molecules":[58],"increase":[59,193],"through":[61,109],"broad":[62],"epigenetic":[63],"perturbations":[64],"cytotoxic":[66],"stress,":[67],"raising":[68],"concerns":[69],"about":[70],"dose-limiting":[71],"cytopenias":[72],"off-target":[74,151],"effects.":[75],"By":[76],"coupling":[77],"single-cell":[78,216],"transcriptomics,":[79],"perturbations,":[81],"functional":[83],"genomics,":[84],"we":[85,167],"identified":[86],"unknown":[88],"role":[89],"neddylation":[91,102,113],"regulation":[94],"fetal":[96],"hemoglobin":[97],"(HbF).":[98],"Partial":[99],"impairment":[100],"cullin":[104,112],"ubiquitin":[105],"ligase":[106],"3":[107],"(CUL3)":[108],"defective":[110],"1":[114],"(DCN1)":[115],"inhibition":[116,137],"leads":[117],"to":[118,218,234],"highly":[119],"selective":[120],"chromatin":[121],"changes,":[122],"histone":[123],"demethylation,":[124],"locus":[127],"binding":[128],"known":[130],"activators":[131],"transcription.":[134],"Further,":[135],"DCN1":[136,178,266],"drives":[138],"switching":[140],"increases":[143],"vitro":[145],"vivo":[148],"with":[149,180,201,223,258],"minimal":[150],"transcriptional":[152],"effects":[153],"no":[155],"evidence":[156],"cytotoxicity":[158],"stress":[160],"erythropoiesis.":[161],"To":[162],"therapeutically":[163],"target":[164,270],"this":[165],"axis,":[166],"report":[168],"discovery":[170],"characterization":[172],"CLY-124,":[174],"a":[175,185,191,204,243,268],"first-in-class,":[176],"covalent":[177],"inhibitor":[179],"favorable":[181],"pharmacology":[182],"properties.":[183],"In":[184],"humanized":[186],"mouse":[187],"model,":[188],"CLY-124":[189,233],"showed":[190],"dose-dependent":[192],"monotherapy":[197],"synergy":[200],"hydroxyurea":[202],"(HU),":[203],"standard":[206],"care.":[208],"Collectively,":[209],"these":[210],"findings":[211],"highlight":[212],"power":[214],"transcriptomics":[217],"elucidate":[219],"undiscovered":[220],"biologic":[221],"insights":[222],"potential,":[225],"promise":[228],"DCN-1":[230],"inhibitors":[231],"like":[232],"address":[235],"\u03b2-hemoglobinopathies.":[236],"With":[237],"appropriate":[239],"nonclinical":[240],"safety":[241],"profile,":[242],"first-in":[244],"human":[245],"study":[246],"safety,":[248],"pharmacokinetics":[249],"assessments":[252],"volunteers":[255],"participants":[257],"SCD":[259],"ongoing":[261],"CLY-124.":[263],"One-sentence":[264],"Summary":[265],"promising":[269],"\u00df-hemoglobinopathies":[272]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-04-26T00:00:00"}