{"id":"https://openalex.org/W7224339589","doi":"https://doi.org/10.26434/chemrxiv.15011217/v1","title":"Protein-State Editing through Proximity-Induced Targeted Delactylation","display_name":"Protein-State Editing through Proximity-Induced Targeted Delactylation","publication_year":2026,"publication_date":"2026-10-28","ids":{"openalex":"https://openalex.org/W7224339589","doi":"https://doi.org/10.26434/chemrxiv.15011217/v1"},"language":"en","primary_location":{"id":"doi:10.26434/chemrxiv.15011217/v1","doi":"https://doi.org/10.26434/chemrxiv.15011217/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15011217/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15011217/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15011217/v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5120315138","display_name":"Meijing Wang","orcid":"https://orcid.org/0000-0003-4067-1127","observed_orcids":["https://orcid.org/0000-0003-4067-1127"]},"institutions":[{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Meijing Wang","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160141790","display_name":"Song Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Song Wang","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5146519454","display_name":"Qingyuan Hu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I103890011","display_name":"Shenyang Pharmaceutical University","ror":"https://ror.org/03dnytd23","country_code":"CN","type":"education","lineage":["https://openalex.org/I103890011"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Qingyuan Hu","raw_affiliation_strings":["Shenyang Pharmaceutical University","Wuya College of Innovation"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shenyang Pharmaceutical University","institution_ids":["https://openalex.org/I103890011"]},{"raw_affiliation_string":"Wuya College of Innovation","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100355812","display_name":"Yang Liu","orcid":"https://orcid.org/0000-0002-1871-6889","observed_orcids":["https://orcid.org/0000-0002-1871-6889"]},"institutions":[{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yang Liu","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160085806","display_name":"Peixi Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Peixi Zhang","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160127831","display_name":"Jing Liang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I103890011","display_name":"Shenyang Pharmaceutical University","ror":"https://ror.org/03dnytd23","country_code":"CN","type":"education","lineage":["https://openalex.org/I103890011"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jing Liang","raw_affiliation_strings":["Shenyang Pharmaceutical University","Wuya College of Innovation"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shenyang Pharmaceutical University","institution_ids":["https://openalex.org/I103890011"]},{"raw_affiliation_string":"Wuya College of Innovation","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160126463","display_name":"Jingtao He","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jingtao He","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100344257","display_name":"Hua Li","orcid":"https://orcid.org/0000-0003-1903-836X","observed_orcids":["https://orcid.org/0000-0003-1903-836X"]},"institutions":[{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Hua Li","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine"],"raw_orcid":"https://orcid.org/0000-0003-1903-836X","affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5121163316","display_name":"Lixia Chen","orcid":"https://orcid.org/0000-0003-2196-1428","observed_orcids":["https://orcid.org/0000-0003-2196-1428"]},"institutions":[{"id":"https://openalex.org/I103890011","display_name":"Shenyang Pharmaceutical University","ror":"https://ror.org/03dnytd23","country_code":"CN","type":"education","lineage":["https://openalex.org/I103890011"]},{"id":"https://openalex.org/I118783713","display_name":"Fujian University of Traditional Chinese Medicine","ror":"https://ror.org/05n0qbd70","country_code":"CN","type":"education","lineage":["https://openalex.org/I118783713"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Lixia Chen","raw_affiliation_strings":["College of Pharmacy","Fujian University of Traditional Chinese Medicine","Shenyang Pharmaceutical University","Wuya College of Innovation"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Pharmacy","institution_ids":[]},{"raw_affiliation_string":"Fujian University of Traditional Chinese Medicine","institution_ids":["https://openalex.org/I118783713"]},{"raw_affiliation_string":"Shenyang Pharmaceutical University","institution_ids":["https://openalex.org/I103890011"]},{"raw_affiliation_string":"Wuya College of Innovation","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"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/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.5723000168800354,"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/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.5723000168800354,"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/T12534","display_name":"Protein Degradation and Inhibitors","score":0.26829999685287476,"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/T12065","display_name":"Hippo pathway signaling and YAP/TAZ","score":0.05620000138878822,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/lactylation","display_name":"lactylation","score":0.9419999718666077},{"id":"https://openalex.org/keywords/histone-deacetylase","display_name":"histone deacetylase","score":0.8759999871253967},{"id":"https://openalex.org/keywords/heterobifunctional-molecules","display_name":"heterobifunctional molecules","score":0.7590000033378601},{"id":"https://openalex.org/keywords/yap","display_name":"YAP","score":0.7739999890327454},{"id":"https://openalex.org/keywords/tead1","display_name":"TEAD1","score":0.9369999766349792},{"id":"https://openalex.org/keywords/post-translational-modification","display_name":"post-translational modification","score":0.5669999718666077},{"id":"https://openalex.org/keywords/gastric-cancer","display_name":"gastric cancer","score":0.6499999761581421},{"id":"https://openalex.org/keywords/liver-cancer","display_name":"liver cancer","score":0.9750000238418579},{"id":"https://openalex.org/keywords/tumor-cell-proliferation","display_name":"tumor cell proliferation","score":0.5170000195503235}],"concepts":[{"id":"https://openalex.org/C71829478","wikidata":"https://www.wikidata.org/wiki/Q901305","display_name":"Immunoprecipitation","level":3,"score":0.5863999724388123},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4805999994277954},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.46459999680519104},{"id":"https://openalex.org/C16613235","wikidata":"https://www.wikidata.org/wiki/Q285982","display_name":"Endogeny","level":2,"score":0.439300000667572},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.4372999966144562},{"id":"https://openalex.org/C171852809","wikidata":"https://www.wikidata.org/wiki/Q731154","display_name":"Chemical biology","level":2,"score":0.4293999969959259},{"id":"https://openalex.org/C2780557392","wikidata":"https://www.wikidata.org/wiki/Q523796","display_name":"Linker","level":2,"score":0.4228000044822693},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4115000069141388},{"id":"https://openalex.org/C119157956","wikidata":"https://www.wikidata.org/wiki/Q796604","display_name":"Acetylation","level":3,"score":0.40459999442100525},{"id":"https://openalex.org/C77445288","wikidata":"https://www.wikidata.org/wiki/Q637488","display_name":"Coactivator","level":4,"score":0.4041000008583069},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3970000147819519},{"id":"https://openalex.org/C123894998","wikidata":"https://www.wikidata.org/wiki/Q425158","display_name":"Fusion protein","level":4,"score":0.38370001316070557},{"id":"https://openalex.org/C2780430158","wikidata":"https://www.wikidata.org/wiki/Q7685902","display_name":"Target protein","level":3,"score":0.35249999165534973},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.3328999876976013},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.33180001378059387},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.32820001244544983},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.30869999527931213},{"id":"https://openalex.org/C2780443040","wikidata":"https://www.wikidata.org/wiki/Q3737863","display_name":"Bifunctional","level":3,"score":0.29510000348091125},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.29089999198913574},{"id":"https://openalex.org/C54757728","wikidata":"https://www.wikidata.org/wiki/Q3511067","display_name":"Nuclear export signal","level":4,"score":0.2904999852180481},{"id":"https://openalex.org/C6929976","wikidata":"https://www.wikidata.org/wiki/Q3771881","display_name":"Regulator","level":3,"score":0.28049999475479126},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.27959999442100525},{"id":"https://openalex.org/C27153228","wikidata":"https://www.wikidata.org/wiki/Q3787274","display_name":"Transcriptional regulation","level":4,"score":0.2662000060081482},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.26570001244544983},{"id":"https://openalex.org/C134320426","wikidata":"https://www.wikidata.org/wiki/Q901026","display_name":"Chromatin immunoprecipitation","level":5,"score":0.2590000033378601},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.25859999656677246}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.26434/chemrxiv.15011217/v1","doi":"https://doi.org/10.26434/chemrxiv.15011217/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15011217/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15011217/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.26434/chemrxiv.15011217/v1","doi":"https://doi.org/10.26434/chemrxiv.15011217/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15011217/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15011217/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.46810001134872437}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7224339589.pdf","grobid_xml":"https://content.openalex.org/works/W7224339589.grobid-xml"},"referenced_works_count":18,"referenced_works":["https://openalex.org/W1864559892","https://openalex.org/W1967434207","https://openalex.org/W2094383719","https://openalex.org/W2340883705","https://openalex.org/W3083451169","https://openalex.org/W3125847651","https://openalex.org/W3165173500","https://openalex.org/W3204435125","https://openalex.org/W4220670155","https://openalex.org/W4221082279","https://openalex.org/W4225364558","https://openalex.org/W4315710006","https://openalex.org/W4393055825","https://openalex.org/W4401917794","https://openalex.org/W4405035291","https://openalex.org/W4408303353","https://openalex.org/W4413019576","https://openalex.org/W4415773287"],"related_works":["https://openalex.org/W4226529856","https://openalex.org/W7203541170","https://openalex.org/W7151285131","https://openalex.org/W4406808279","https://openalex.org/W4408802515","https://openalex.org/W4413110426","https://openalex.org/W4411026094","https://openalex.org/W4415923665","https://openalex.org/W4220670155","https://openalex.org/W2284223727"],"abstract_inverted_index":{"Selective":[0],"manipulation":[1],"of":[2,28,48,75,105,151,162,172,180,198],"protein":[3,17,120,199],"post-translational":[4],"modifications":[5],"without":[6,114,209],"eliminating":[7],"the":[8,52,173,178,181],"modified":[9],"proteins":[10,40],"represents":[11],"an":[12],"emerging":[13],"strategy":[14,194],"for":[15,195,205],"controlling":[16],"function.":[18],"Here,":[19],"we":[20,50,71],"introduce":[21],"Delactylation":[22],"Targeting":[23],"Chimeras":[24],"(DeLacTACs),":[25],"a":[26,46,73,191,203],"class":[27],"heterobifunctional":[29],"molecules":[30],"designed":[31],"to":[32],"redirect":[33],"endogenous":[34,131],"histone":[35],"deacetylases":[36],"(HDACs)":[37],"toward":[38],"lactylated":[39],"through":[41],"chemically":[42],"induced":[43],"proximity.":[44],"As":[45],"proof":[47],"concept,":[49],"targeted":[51,196],"oncogenic":[53],"transcriptional":[54,107],"coactivator":[55],"YAP,":[56],"whose":[57],"lactylation":[58,104,200],"at":[59,110],"Lys90":[60],"promotes":[61],"YAP\u2013TEAD":[62],"signaling.":[63],"Through":[64],"modular":[65],"synthesis":[66],"and":[67,77,80,87,92,112,130,157,159,165,201],"systematic":[68],"linker":[69],"optimization,":[70],"developed":[72],"series":[74],"DeLacTACs":[76,189],"identified":[78],"Y3CH":[79],"Y1PH":[81],"as":[82,190],"active":[83],"compounds":[84],"in":[85,117],"gastric":[86],"liver":[88],"cancer":[89],"cells.":[90],"Immunoprecipitation":[91],"quantitative":[93],"mass":[94],"spectrometry":[95],"demonstrated":[96],"reduced":[97,143],"YAP":[98,129,144],"K90":[99],"lactylation,":[100],"accompanied":[101,141],"by":[102,142],"decreased":[103],"its":[106],"partner":[108],"TEAD1":[109],"Lys108":[111],"Lys57,":[113],"substantial":[115],"changes":[116,139],"their":[118],"total":[119],"abundance.":[121],"Co-immunoprecipitation":[122],"experiments":[123],"further":[124],"supported":[125],"enhanced":[126],"association":[127],"between":[128],"HDAC":[132],"machinery":[133],"following":[134],"DeLacTAC":[135],"treatment.":[136],"These":[137],"molecular":[138,183],"were":[140],"nuclear":[145],"accumulation,":[146],"attenuated":[147],"YAP\u2013TEAD1":[148],"colocalization,":[149],"suppression":[150],"downstream":[152],"genes":[153],"including":[154],"CTGF,":[155],"CYR61,":[156],"AARS1,":[158],"pronounced":[160],"inhibition":[161],"tumor-cell":[163],"proliferation":[164],"colony":[166],"formation.":[167],"The":[168],"substantially":[169],"weaker":[170],"effects":[171],"individual":[174],"recognition":[175],"components":[176],"highlighted":[177],"importance":[179],"bifunctional":[182],"architecture.":[184],"Together,":[185],"these":[186],"findings":[187],"establish":[188],"proximity-based":[192],"chemical":[193],"modulation":[197],"provide":[202],"foundation":[204],"programmable":[206],"protein-state":[207],"editing":[208],"target":[210],"degradation.":[211]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-30T00:00:00"}