{"id":"https://openalex.org/W4390765658","doi":"https://doi.org/10.2337/db23-0506","title":"KD025 Is a Casein Kinase 2 Inhibitor That Protects Against Glucolipotoxicity in \u03b2-Cells","display_name":"KD025 Is a Casein Kinase 2 Inhibitor That Protects Against Glucolipotoxicity in \u03b2-Cells","publication_year":2024,"publication_date":"2024-01-11","ids":{"openalex":"https://openalex.org/W4390765658","doi":"https://doi.org/10.2337/db23-0506","pmid":"https://pubmed.ncbi.nlm.nih.gov/38211571","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/10958584"},"language":"en","primary_location":{"id":"doi:10.2337/db23-0506","doi":"https://doi.org/10.2337/db23-0506","is_oa":false,"landing_page_url":"https://doi.org/10.2337/db23-0506","pdf_url":null,"source":{"id":"https://openalex.org/S129060628","display_name":"Diabetes","issn_l":"0012-1797","issn":["0012-1797","1939-327X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320274","host_organization_name":"American Diabetes Association","host_organization_lineage":["https://openalex.org/P4310320274"],"host_organization_lineage_names":["American Diabetes Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10958584","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5054904715","display_name":"Ranjan Devkota","orcid":"https://orcid.org/0009-0001-6289-7891","observed_orcids":["https://orcid.org/0009-0001-6289-7891"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ranjan Devkota","raw_affiliation_strings":["Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003206715","display_name":"Jonnell Candice Small","orcid":"https://orcid.org/0000-0002-2335-6873","observed_orcids":["https://orcid.org/0000-0002-2335-6873"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jonnell C. Small","raw_affiliation_strings":["Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026509943","display_name":"Kaycee Carbone","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kaycee Carbone","raw_affiliation_strings":["Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044292565","display_name":"Michael A. Glass","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael A. Glass","raw_affiliation_strings":["Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5024102434","display_name":"Amedeo Vetere","orcid":"https://orcid.org/0000-0001-5608-0773","observed_orcids":["https://orcid.org/0000-0001-5608-0773"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Amedeo Vetere","raw_affiliation_strings":["Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA","institution_ids":["https://openalex.org/I107606265"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5075249814","display_name":"Bridget K. Wagner","orcid":"https://orcid.org/0000-0002-2629-361X","observed_orcids":["https://orcid.org/0000-0002-2629-361X"]},"institutions":[{"id":"https://openalex.org/I107606265","display_name":"Broad Institute","ror":"https://ror.org/05a0ya142","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I107606265"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Bridget K. Wagner","raw_affiliation_strings":["Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA"],"raw_orcid":"https://orcid.org/0000-0002-2629-361X","affiliations":[{"raw_affiliation_string":"Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA","institution_ids":["https://openalex.org/I107606265"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5075249814"],"corresponding_institution_ids":["https://openalex.org/I107606265"],"apc_list":null,"apc_paid":null,"fwci":2.5132,"has_fulltext":false,"cited_by_count":6,"citation_normalized_percentile":{"value":0.8814726,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":97},"biblio":{"volume":"73","issue":"4","first_page":"585","last_page":"591"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10839","display_name":"Pancreatic function and diabetes","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"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/T10839","display_name":"Pancreatic function and diabetes","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"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/T10401","display_name":"Diabetes Treatment and Management","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"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/T11150","display_name":"Endoplasmic Reticulum Stress and Disease","score":0.0003000000142492354,"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/casein-kinase-2","display_name":"casein kinase 2","score":0.9700000286102295},{"id":"https://openalex.org/keywords/glucolipotoxicity","display_name":"glucolipotoxicity","score":0.9150000214576721},{"id":"https://openalex.org/keywords/pancreatic-beta-cells","display_name":"pancreatic beta cells","score":0.7310000061988831},{"id":"https://openalex.org/keywords/type-2-diabetes","display_name":"type 2 diabetes","score":0.8209999799728394},{"id":"https://openalex.org/keywords/rock2","display_name":"ROCK2","score":0.6919999718666077},{"id":"https://openalex.org/keywords/islet-viability","display_name":"islet viability","score":0.546999990940094}],"concepts":[{"id":"https://openalex.org/C143910341","wikidata":"https://www.wikidata.org/wiki/Q21102140","display_name":"Casein kinase 2","level":5,"score":0.9217511415481567},{"id":"https://openalex.org/C205744416","wikidata":"https://www.wikidata.org/wiki/Q18248555","display_name":"Casein kinase 2, alpha 1","level":5,"score":0.7033274173736572},{"id":"https://openalex.org/C160110348","wikidata":"https://www.wikidata.org/wiki/Q5048387","display_name":"Casein kinase 1","level":4,"score":0.6393528580665588},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.6216719150543213},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.6000455617904663},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5183535814285278},{"id":"https://openalex.org/C59143045","wikidata":"https://www.wikidata.org/wiki/Q15314942","display_name":"Cyclin-dependent kinase 9","level":5,"score":0.5064891576766968},{"id":"https://openalex.org/C2775880066","wikidata":"https://www.wikidata.org/wiki/Q186521","display_name":"Threonine","level":4,"score":0.46671149134635925},{"id":"https://openalex.org/C2776414213","wikidata":"https://www.wikidata.org/wiki/Q183290","display_name":"Serine","level":3,"score":0.45599693059921265},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.454983651638031},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4266927242279053},{"id":"https://openalex.org/C82495950","wikidata":"https://www.wikidata.org/wiki/Q14911732","display_name":"Cyclin-dependent kinase 2","level":4,"score":0.39354366064071655},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3744765520095825},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.3743130564689636}],"mesh":[{"descriptor_ui":"D003924","descriptor_name":"Diabetes Mellitus, Type 2","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D006576","descriptor_name":"Heterocyclic Compounds, 4 or More Rings","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047390","descriptor_name":"Casein Kinase II","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D050417","descriptor_name":"Insulin-Secreting Cells","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":4,"locations":[{"id":"doi:10.2337/db23-0506","doi":"https://doi.org/10.2337/db23-0506","is_oa":false,"landing_page_url":"https://doi.org/10.2337/db23-0506","pdf_url":null,"source":{"id":"https://openalex.org/S129060628","display_name":"Diabetes","issn_l":"0012-1797","issn":["0012-1797","1939-327X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320274","host_organization_name":"American Diabetes Association","host_organization_lineage":["https://openalex.org/P4310320274"],"host_organization_lineage_names":["American Diabetes Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:10767993","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10958584","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:10958584","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10958584","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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"Text"},{"id":"pmid:38211571","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/38211571","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":"Diabetes","raw_type":"Journal Article"}],"best_oa_location":{"id":"pmh:oai:europepmc.org:10767993","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10958584","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":null,"raw_type":"Text"},"sustainable_development_goals":[{"score":0.9763000011444092,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1035330972","display_name":"One-compound, one-islet: A high-throughput platform for small-molecule discovery","funder_award_id":"U01DK123717","funder_id":"https://openalex.org/F4320337357","funder_display_name":"National Institute of Diabetes and Digestive and Kidney Diseases"},{"id":"https://openalex.org/G1623854956","display_name":"Opera Phenix high-throughput microplate confocal imager for high-content screening","funder_award_id":"1s10od026839-01","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G5986421188","display_name":null,"funder_award_id":"U01DK123717","funder_id":"https://openalex.org/F4320317722","funder_display_name":"Human Islet Research Network"},{"id":"https://openalex.org/G6698273445","display_name":null,"funder_award_id":"KAW 2019.0580","funder_id":"https://openalex.org/F4320322327","funder_display_name":"Knut och Alice Wallenbergs Stiftelse"}],"funders":[{"id":"https://openalex.org/F4320317722","display_name":"Human Islet Research Network","ror":null},{"id":"https://openalex.org/F4320322327","display_name":"Knut och Alice Wallenbergs Stiftelse","ror":"https://ror.org/004hzzk67"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337357","display_name":"National Institute of Diabetes and Digestive and Kidney Diseases","ror":"https://ror.org/00adh9b73"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":24,"referenced_works":["https://openalex.org/W44929223","https://openalex.org/W2000050828","https://openalex.org/W2024264816","https://openalex.org/W2081595122","https://openalex.org/W2088938650","https://openalex.org/W2093611899","https://openalex.org/W2101369715","https://openalex.org/W2118068371","https://openalex.org/W2122929112","https://openalex.org/W2142933851","https://openalex.org/W2188225742","https://openalex.org/W2233428981","https://openalex.org/W2614899983","https://openalex.org/W2742668309","https://openalex.org/W2971942600","https://openalex.org/W2980342819","https://openalex.org/W2993211903","https://openalex.org/W3007853433","https://openalex.org/W3021807193","https://openalex.org/W3162383196","https://openalex.org/W3192763356","https://openalex.org/W4210880335","https://openalex.org/W4224243253","https://openalex.org/W4254445254"],"related_works":["https://openalex.org/W4390731821","https://openalex.org/W4224243253","https://openalex.org/W3007853433","https://openalex.org/W7070424422","https://openalex.org/W3024887787","https://openalex.org/W2075640803","https://openalex.org/W4406057968","https://openalex.org/W4296274439","https://openalex.org/W2742668309","https://openalex.org/W2002427009"],"abstract_inverted_index":{"Glucolipotoxicity":[0],"(GLT),":[1],"in":[2,26,60],"which":[3],"elevated":[4],"levels":[5],"of":[6,22,28,34,49,72,74,83,92,106,122,124,128],"glucose":[7],"and":[8,63,80],"fatty":[9],"acids":[10],"have":[11],"deleterious":[12],"effects":[13,91],"on":[14],"\u03b2-cell":[15],"biology,":[16],"is":[17],"thought":[18],"to":[19,149],"be":[20],"one":[21,123],"the":[23,70,89,120,125],"major":[24],"contributors":[25],"progression":[27],"type":[29],"2":[30,54,109],"diabetes.":[31],"In":[32],"search":[33],"novel":[35],"small":[36],"molecules":[37],"that":[38,78,100,119,145],"protect":[39,150],"\u03b2-cells":[40,151],"against":[41,94],"GLT,":[42],"we":[43,76],"previously":[44],"discovered":[45],"KD025,":[46,75],"an":[47],"inhibitor":[48],"Rho-associated":[50],"coiled-coil-containing":[51],"kinase":[52,97,108,130],"isoform":[53],"(ROCK2),":[55],"as":[56],"a":[57,111],"GLT-protective":[58],"compound":[59],"INS-1E":[61],"cells":[62],"dissociated":[64],"human":[65],"islets.":[66],"To":[67],"further":[68],"understand":[69],"mechanism":[71],"action":[73],"found":[77],"pharmacological":[79],"genetic":[81],"inhibition":[82,121],"ROCK2":[84],"was":[85],"not":[86,134],"responsible":[87],"for":[88],"protective":[90],"KD025":[93,101,146],"GLT.":[95,142,153],"Instead,":[96],"profiling":[98],"revealed":[99],"potently":[102],"inhibits":[103,147],"catalytic":[104,126],"subunits":[105,127],"casein":[107,129],"(CK2),":[110],"constitutively":[112],"active":[113],"serine/threonine":[114],"kinase.":[115],"We":[116,143],"experimentally":[117],"verified":[118],"2,":[131],"CK2A1,":[132],"but":[133],"CK2A2,":[135],"improved":[136],"cell":[137],"viability":[138],"when":[139],"challenged":[140],"with":[141],"conclude":[144],"CK2":[148],"from":[152]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2024-01-13T00:00:00"}