{"id":"https://openalex.org/W7225262383","doi":"https://doi.org/10.6084/m9.figshare.34912717","title":"Identification, optimisation, and structural elucidation of chloroacetamide scaffold as covalent inhibitors for ubiquitin C-terminal Hydrolase L3","display_name":"Identification, optimisation, and structural elucidation of chloroacetamide scaffold as covalent inhibitors for ubiquitin C-terminal Hydrolase L3","publication_year":2026,"publication_date":"2026-11-04","ids":{"openalex":"https://openalex.org/W7225262383","doi":"https://doi.org/10.6084/m9.figshare.34912717"},"language":"en","primary_location":{"id":"doi:10.6084/m9.figshare.34912717","doi":"https://doi.org/10.6084/m9.figshare.34912717","is_oa":true,"landing_page_url":"https://doi.org/10.6084/m9.figshare.34912717","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.6084/m9.figshare.34912717","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5048616037","display_name":"Nagabhushana C. Beeralingappa","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nagabhushana C. Beeralingappa","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043518045","display_name":"Mengyao Lu","orcid":"https://orcid.org/0000-0002-4338-8418","observed_orcids":["https://orcid.org/0000-0002-4338-8418"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mengyao Lu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160593382","display_name":"Rishi Patel","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rishi Patel","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160639568","display_name":"Nipuni Pannala","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nipuni Pannala","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083271106","display_name":"Alisha Dhiman","orcid":"https://orcid.org/0000-0002-4395-9292","observed_orcids":["https://orcid.org/0000-0002-4395-9292"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alisha Dhiman","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074248094","display_name":"Brittany N. Heil","orcid":"https://orcid.org/0000-0001-8892-8564","observed_orcids":["https://orcid.org/0000-0001-8892-8564"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Brittany N. Heil","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082208174","display_name":"Ryan D. Imhoff","orcid":"https://orcid.org/0000-0002-8510-8437","observed_orcids":["https://orcid.org/0000-0002-8510-8437"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ryan D. Imhoff","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159972342","display_name":"Emily G. Smith","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Emily G. Smith","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5137356520","display_name":"Mei B Bahler","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mei B. Bahler","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5137332351","display_name":"Haley L Marsden","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Haley L. Marsden","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052134233","display_name":"Brittany L. Allen-Petersen","orcid":"https://orcid.org/0000-0002-7436-9412","observed_orcids":["https://orcid.org/0000-0002-7436-9412"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Brittany L. Allen-Petersen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090843213","display_name":"Michael K. Wendt","orcid":"https://orcid.org/0000-0002-3665-7413","observed_orcids":["https://orcid.org/0000-0002-3665-7413"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael K. Wendt","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160641836","display_name":"Chittaranjan Das","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chittaranjan Das","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5054207395","display_name":"Daniel Patrick Flaherty","orcid":"https://orcid.org/0000-0002-8305-0606","observed_orcids":["https://orcid.org/0000-0002-8305-0606"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Daniel P. Flaherty","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.73456816,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"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/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.9955999851226807,"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/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.9955999851226807,"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":0.003700000001117587,"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/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":9.999999747378752e-05,"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/uchl3","display_name":"UCHL3","score":0.9729999899864197},{"id":"https://openalex.org/keywords/deubiquitinase","display_name":"deubiquitinase","score":0.824999988079071},{"id":"https://openalex.org/keywords/covalent-inhibitors","display_name":"covalent inhibitors","score":0.9539999961853027},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.7580000162124634},{"id":"https://openalex.org/keywords/dna-damage-response","display_name":"DNA damage response","score":0.753000020980835},{"id":"https://openalex.org/keywords/cancer-therapy-targets","display_name":"cancer therapy targets","score":0.6759999990463257},{"id":"https://openalex.org/keywords/chemical-probes","display_name":"chemical probes","score":0.8130000233650208}],"concepts":[{"id":"https://openalex.org/C102658986","wikidata":"https://www.wikidata.org/wiki/Q5266092","display_name":"Deubiquitinating enzyme","level":4,"score":0.882099986076355},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.7497000098228455},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7486000061035156},{"id":"https://openalex.org/C2780120296","wikidata":"https://www.wikidata.org/wiki/Q96286","display_name":"Hydrolase","level":3,"score":0.6571999788284302},{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.6380000114440918},{"id":"https://openalex.org/C2779201268","wikidata":"https://www.wikidata.org/wiki/Q186474","display_name":"Cysteine","level":3,"score":0.5785999894142151},{"id":"https://openalex.org/C89429830","wikidata":"https://www.wikidata.org/wiki/Q735710","display_name":"Scaffold","level":2,"score":0.5633000135421753},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5435000061988831},{"id":"https://openalex.org/C53645450","wikidata":"https://www.wikidata.org/wiki/Q907093","display_name":"Scaffold protein","level":3,"score":0.43619999289512634},{"id":"https://openalex.org/C108204754","wikidata":"https://www.wikidata.org/wiki/Q353392","display_name":"Adduct","level":2,"score":0.4293000102043152},{"id":"https://openalex.org/C118792377","wikidata":"https://www.wikidata.org/wiki/Q108584245","display_name":"Selectivity","level":3,"score":0.42669999599456787},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.41749998927116394},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.40400001406669617},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.3774000108242035},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.35989999771118164},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.3431999981403351},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.33390000462532043},{"id":"https://openalex.org/C171852809","wikidata":"https://www.wikidata.org/wiki/Q731154","display_name":"Chemical biology","level":2,"score":0.31299999356269836},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.305400013923645},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.30219998955726624},{"id":"https://openalex.org/C193042331","wikidata":"https://www.wikidata.org/wiki/Q1772003","display_name":"Structure\u2013activity relationship","level":3,"score":0.29910001158714294},{"id":"https://openalex.org/C2780430158","wikidata":"https://www.wikidata.org/wiki/Q7685902","display_name":"Target protein","level":3,"score":0.2928999960422516},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.29120001196861267},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.2849000096321106},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.2777999937534332},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.27639999985694885},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.2709999978542328},{"id":"https://openalex.org/C2776192174","wikidata":"https://www.wikidata.org/wiki/Q18028978","display_name":"Mdm2","level":3,"score":0.2700999975204468},{"id":"https://openalex.org/C182561583","wikidata":"https://www.wikidata.org/wiki/Q7876535","display_name":"Ubiquitin-conjugating enzyme","level":5,"score":0.26980000734329224},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.2653000056743622},{"id":"https://openalex.org/C2777864359","wikidata":"https://www.wikidata.org/wiki/Q5090466","display_name":"Chemical genetics","level":3,"score":0.26510000228881836},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.2597000002861023},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.25920000672340393},{"id":"https://openalex.org/C114373084","wikidata":"https://www.wikidata.org/wiki/Q273499","display_name":"Chemical synthesis","level":3,"score":0.258899986743927},{"id":"https://openalex.org/C2776376580","wikidata":"https://www.wikidata.org/wiki/Q407355","display_name":"Transferase","level":3,"score":0.2572999894618988},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.25119999051094055}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.6084/m9.figshare.34912717","doi":"https://doi.org/10.6084/m9.figshare.34912717","is_oa":true,"landing_page_url":"https://doi.org/10.6084/m9.figshare.34912717","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},{"id":"doi:10.6084/m9.figshare.34912717.v1","doi":"https://doi.org/10.6084/m9.figshare.34912717.v1","is_oa":true,"landing_page_url":"https://doi.org/10.6084/m9.figshare.34912717.v1","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"}],"best_oa_location":{"id":"doi:10.6084/m9.figshare.34912717","doi":"https://doi.org/10.6084/m9.figshare.34912717","is_oa":true,"landing_page_url":"https://doi.org/10.6084/m9.figshare.34912717","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4392849504","https://openalex.org/W2071146082","https://openalex.org/W4404633702","https://openalex.org/W3210138755","https://openalex.org/W4206574168","https://openalex.org/W3131313991","https://openalex.org/W3110515702","https://openalex.org/W2035186247","https://openalex.org/W3037707446","https://openalex.org/W6963821610"],"abstract_inverted_index":{"The":[0,67,108],"deubiquitinating":[1],"enzyme,":[2],"ubiquitin":[3,95],"C-terminal":[4],"hydrolase":[5],"L3":[6],"(UCHL3),":[7],"has":[8,31],"been":[9,32],"implicated":[10],"as":[11,110],"a":[12,19,39,59,94,111,114],"potential":[13],"therapeutic":[14],"target":[15,30,47],"for":[16],"cancer":[17],"with":[18,82,102],"role":[20],"in":[21,104,128],"regulating":[22],"the":[23,29,83,87,118],"DNA":[24],"damage":[25],"response":[26],"pathways.":[27],"While":[28],"studied":[33],"using":[34,93],"genetic":[35],"methods":[36],"there":[37],"is":[38],"lack":[40],"of":[41,58,86,117],"reliable":[42],"chemical":[43,61],"probes":[44],"to":[45,125],"selectivity":[46],"UCHL3.":[48,66],"In":[49],"this":[50],"study":[51],"we":[52,98],"report":[53],"hit":[54],"identification":[55],"and":[56],"optimisation":[57],"new":[60,119],"scaffold":[62,120],"that":[63,77,121],"irreversibly":[64],"inhibits":[65],"observed":[68],"structure-activity":[69],"relationships":[70],"are":[71],"corroborated":[72],"by":[73],"ligand-bound":[74],"crystal":[75],"structures":[76],"confirm":[78],"covalent":[79],"adduct":[80],"formation":[81],"catalytic":[84],"cysteine":[85],"enzyme.":[88],"Finally,":[89],"through":[90],"gel-shift":[91],"assays":[92],"activity-based":[96],"probe":[97,126],"demonstrate":[99],"on-target":[100],"engagement":[101],"UCHL3":[103,127],"two":[105],"cell":[106],"lines.":[107],"work":[109],"whole":[112],"presents":[113],"comprehensive":[115],"evaluation":[116],"can":[122],"be":[123],"utilised":[124],"different":[129],"biological":[130],"contexts.":[131]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2026-11-05T00:00:00"}