{"id":"https://openalex.org/W7052500176","doi":null,"title":"Screening of Covalent Kinase Inhibitors Yields Hits for Cysteine Protease USP7 / HAUSP","display_name":"Screening of Covalent Kinase Inhibitors Yields Hits for Cysteine Protease USP7 / HAUSP","publication_year":2025,"publication_date":"2025-03-01","ids":{"openalex":"https://openalex.org/W7052500176"},"language":"en","primary_location":{"id":"pmh:oai:doaj.org/article:c11bfa711ec14b3e9658f48804ef28fc","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/c11bfa711ec14b3e9658f48804ef28fc","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":"Drug Design, Development and Therapy, Vol Volume 19, Pp 2253-2284 (2025)","raw_type":"article"},"volume":null,"type":"article","indexed_in":["doaj"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doaj.org/article/c11bfa711ec14b3e9658f48804ef28fc","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Ernst LN","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ernst LN","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011877713","display_name":"Simon Jaag","orcid":"https://orcid.org/0000-0002-3847-774X","observed_orcids":["https://orcid.org/0000-0002-3847-774X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jaag SJ","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048439457","display_name":"Valentin R. Wydra","orcid":"https://orcid.org/0009-0004-3295-0526","observed_orcids":["https://orcid.org/0009-0004-3295-0526"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Wydra VR","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074312384","display_name":"Benedikt Masberg","orcid":"https://orcid.org/0000-0003-2041-4983","observed_orcids":["https://orcid.org/0000-0003-2041-4983"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Masberg B","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Knappe C","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Knappe C","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049077715","display_name":"Stefan Gerstenecker","orcid":"https://orcid.org/0000-0002-7658-9945","observed_orcids":["https://orcid.org/0000-0002-7658-9945"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gerstenecker S","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056348058","display_name":"Ricardo A. M. Serafim","orcid":"https://orcid.org/0000-0003-0614-1798","observed_orcids":["https://orcid.org/0000-0003-0614-1798"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Serafim RAM","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Liang XJ","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Liang XJ","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5092557879","display_name":"Nico J. Seidler","orcid":"https://orcid.org/0009-0007-4405-2397","observed_orcids":["https://orcid.org/0009-0007-4405-2397"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Seidler NJ","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"L\u00e4mmerhofer M","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"L\u00e4mmerhofer M","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5021605039","display_name":"Matthias Gehringer","orcid":"https://orcid.org/0000-0003-0163-3419","observed_orcids":["https://orcid.org/0000-0003-0163-3419"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gehringer M","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5086525697","display_name":"Frank M. Boeckler","orcid":"https://orcid.org/0000-0001-8738-6716","observed_orcids":["https://orcid.org/0000-0001-8738-6716"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Boeckler FM","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":0.28569608,"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":true,"primary_topic":{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.9535999894142151,"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":0.9535999894142151,"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":0.027799999341368675,"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/T10620","display_name":"Protease and Inhibitor Mechanisms","score":0.004399999976158142,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/usp7","display_name":"USP7","score":0.9959999918937683},{"id":"https://openalex.org/keywords/ubiquitin-specific-protease","display_name":"ubiquitin-specific protease","score":0.7789999842643738},{"id":"https://openalex.org/keywords/covalent-kinase-inhibitors","display_name":"covalent kinase inhibitors","score":0.9769999980926514},{"id":"https://openalex.org/keywords/p53-signaling-pathway","display_name":"p53 pathway","score":0.5879999995231628},{"id":"https://openalex.org/keywords/tumor-suppressor-genes","display_name":"tumor suppressor","score":0.5839999914169312},{"id":"https://openalex.org/keywords/hit-identification","display_name":"hit identification","score":0.5400000214576721},{"id":"https://openalex.org/keywords/virtual-screening","display_name":"virtual screening","score":0.4729999899864197},{"id":"https://openalex.org/keywords/molecular-docking","display_name":"molecular docking","score":0.4819999933242798},{"id":"https://openalex.org/keywords/molecular-dynamics-simulation","display_name":"molecular dynamics simulation","score":0.47600001096725464},{"id":"https://openalex.org/keywords/protein-ligand-interactions","display_name":"protein-ligand interactions","score":0.4620000123977661},{"id":"https://openalex.org/keywords/ubiquitin-c-terminal-hydrolase","display_name":"ubiquitin C-terminal hydrolase","score":0.492000013589859},{"id":"https://openalex.org/keywords/anticancer-drug-discovery","display_name":"anticancer drug discovery","score":0.4729999899864197},{"id":"https://openalex.org/keywords/small-molecule-inhibitors","display_name":"small molecule inhibitors","score":0.4350000023841858}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5830000042915344},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.3549000024795532},{"id":"https://openalex.org/C2777283782","wikidata":"https://www.wikidata.org/wiki/Q419343","display_name":"Cysteine protease","level":4,"score":0.34619998931884766},{"id":"https://openalex.org/C103697762","wikidata":"https://www.wikidata.org/wiki/Q4112105","display_name":"Virtual screening","level":3,"score":0.3407000005245209},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.328900009393692},{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.27469998598098755},{"id":"https://openalex.org/C178855305","wikidata":"https://www.wikidata.org/wiki/Q614304","display_name":"Pharmaceutical sciences","level":2,"score":0.2728999853134155},{"id":"https://openalex.org/C2776714187","wikidata":"https://www.wikidata.org/wiki/Q212410","display_name":"Protease","level":3,"score":0.26499998569488525},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.2508000135421753},{"id":"https://openalex.org/C104863432","wikidata":"https://www.wikidata.org/wiki/Q614304","display_name":"Pharmacy","level":2,"score":0.24729999899864197}],"mesh":[],"locations_count":1,"locations":[{"id":"pmh:oai:doaj.org/article:c11bfa711ec14b3e9658f48804ef28fc","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/c11bfa711ec14b3e9658f48804ef28fc","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":"Drug Design, Development and Therapy, Vol Volume 19, Pp 2253-2284 (2025)","raw_type":"article"}],"best_oa_location":{"id":"pmh:oai:doaj.org/article:c11bfa711ec14b3e9658f48804ef28fc","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/c11bfa711ec14b3e9658f48804ef28fc","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":"Drug Design, Development and Therapy, Vol Volume 19, Pp 2253-2284 (2025)","raw_type":"article"},"sustainable_development_goals":[{"score":0.5683000087738037,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Larissa":[0],"N":[1],"Ernst,1":[2],"Simon":[3],"J":[4,22],"Jaag,2":[5],"Valentin":[6],"R":[7],"Wydra,3":[8],"Benedikt":[9],"Masberg,2":[10],"Cornelius":[11],"Knappe,2":[12],"Stefan":[13],"Gerstenecker,3":[14],"Ricardo":[15],"AM":[16],"Serafim,3":[17],"Xiaojun":[18],"Julia":[19],"Liang,4,5":[20],"Nico":[21],"Seidler,3,5":[23],"Michael":[24],"L\u00e4mmerhofer,2":[25],"Matthias":[26],"Gehringer,3\u2013":[27],"5":[28],"Frank":[29,139],"M":[30,140],"Boeckler1,6":[31],"1Department":[32],"of":[33,49,56,66,73,83,90,98,108,217,223,241,272,337,346,354,391,399,448],"Pharmacy":[34,57,74],"and":[35,45,58,75,114,146,265,348,365,389,404,415],"Biochemistry,":[36,59,76],"Eberhard":[37,60,77,93,119,132,153],"Karls":[38,61,78,94,120,133,154],"Universit\u00e4t":[39,95,121,134,155],"T\u00fcbingen,":[40,52,69,86,96,104,122,123,135,136,156,161],"Laboratory":[41],"for":[42,101,128,143,150,234,297,305],"Molecular":[43,144],"Design":[44,145],"Pharmaceutical":[46,50,63,67,80,84,151],"Biophysics,":[47,148],"Institute":[48,65,82,100,127,149],"Sciences,":[51,68,85,152],"72076,":[53,70,87,105,124,137,162],"Germany;":[54,71,88,106,125],"2Department":[55],"Universit\u00e4t,":[62,79],"(Bio-)Analysis,":[64],"3Department":[72],"Chemistry,":[81,92],"4Department":[89],"Medicinal":[91],"Faculty":[97],"Medicine,":[99],"Biomedical":[102,129],"Engineering,":[103],"5Cluster":[107],"Excellence":[109],"iFIT":[110],"(EXC":[111],"2180)":[112],"\u2018Image-Guided":[113],"Functionally":[115],"Instructed":[116],"Tumor":[117],"Therapies\u2019,":[118],"6Interfaculty":[126],"Informatics":[130],"(IBMI),":[131],"GermanyCorrespondence:":[138],"Boeckler,":[141],"Lab":[142],"Pharm.":[147],"Auf":[157],"der":[158],"Morgenstelle":[159],"8,":[160],"Germany,":[163],"Tel":[164],"+49":[165],"7071":[166],"29":[167],"74567,":[168],"Email":[169],"frank.boeckler@uni-tuebingen.dePurpose:":[170],"The":[171,293,330,387],"ubiquitin-specific":[172,180],"protease":[173,181],"7":[174],"(USP7),":[175],"also":[176],"known":[177],"as":[178,243,245,280],"herpes-associated":[179],"(HAUSP)":[182],"is":[183],"an":[184,270],"interesting":[185],"target":[186,412],"due":[187],"to":[188,300,428],"its":[189,249,349],"role":[190],"in":[191,207,284,419],"the":[192,238,314,338,343,356,392,411,420],"tumor":[193],"suppressor":[194],"p53":[195],"pathway.":[196],"In":[197],"recent":[198],"years":[199],"targeted":[200],"covalent":[201,224,281,320,358,378,432],"inhibitors":[202,283,450],"have":[203,212,376],"gained":[204],"significant":[205],"importance":[206],"pharmaceutical":[208],"research.":[209],"Thus,":[210],"we":[211],"investigated":[213],"a":[214,285,306,377],"small":[215],"library":[216,394],"129":[218,273,339],"ligands":[219],"bearing":[220],"different":[221],"types":[222],"reactive":[225],"groups":[226],"(\u201cwarheads\u201d)":[227],"from":[228,424],"various":[229],"kinase":[230,282,393,449],"drug":[231],"discovery":[232],"projects":[233],"their":[235,246,298],"reactivity":[236],"towards":[237],"catalytic":[239,315],"cysteine":[240,433],"USP7,":[242],"well":[244],"influence":[247],"on":[248],"melting":[250,344,421],"temperature.":[251],"These":[252],"compounds":[253,275,341],"mainly":[254],"encompassed":[255],"\u03b1,\u03b2-unsaturated":[256],"amides":[257],"specifically":[258],"acrylamides,":[259],"SNAr":[260,402],"reacting":[261],"compounds,":[262],"aryl":[263],"fluorosulfates":[264],"sulfonyl":[266],"fluorides.Methods:":[267],"We":[268],"analyzed":[269],"array":[271],"electrophilic":[274],"which":[276],"had":[277],"been":[278],"designed":[279],"DSF-based":[286],"(differential":[287],"scanning":[288,436],"fluorimetry)":[289],"screen":[290,332],"against":[291],"USP7.":[292],"hits":[294,375,398],"were":[295],"evaluated":[296,323],"ability":[299],"cause":[301],"similar":[302],"thermal":[303],"shifts":[304,418],"CYS-deficient":[307],"USP7":[308,347,367],"control":[309],"mutant":[310,350,366],"(USP7asoc),":[311],"where":[312],"only":[313],"Cys223":[316],"was":[317,322,361],"retained.":[318],"Additionally,":[319],"binding":[321,359],"by":[324,368],"intact":[325,369,439],"protein":[326,370,413,440],"mass":[327,441],"spectrometry":[328],"(MS).Results:":[329],"DSF":[331],"revealed":[333,395],"that,":[334],"predominantly":[335],"18":[336],"tested":[340],"decreased":[342],"temperature":[345],"USP7asoc.":[351],"For":[352],"8":[353],"these,":[355],"hypothesized":[357],"mode":[360],"corroborated":[362],"with":[363],"native":[364],"MS.":[371],"Nearly":[372],"all":[373],"identified":[374],"warhead":[379,407],"that":[380],"reacts":[381],"via":[382],"nucleophilic":[383,443],"aromatic":[384,444],"substitution":[385,445],"(SNAr).Conclusion:":[386],"screening":[388],"evaluation":[390],"several":[396],"initial":[397],"interest.":[400],"Seven":[401],"warheads":[403],"one":[405],"acrylamide":[406],"compound":[408],"covalently":[409],"modified":[410],"(USP7)":[414],"showed":[416],"clear":[417],"temperatures":[422],"ranging":[423],"\u2212":[425],"6.0":[426],"\u00b0C":[427],"+1.7":[429],"\u00b0C.":[430],"Keywords:":[431],"modification,":[434],"differential":[435],"fluorimetry":[437],"(DSF),":[438],"spectrometry,":[442],"(SNAr),":[446],"repurposing":[447]},"counts_by_year":[],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2025-10-10T00:00:00"}