{"id":"https://openalex.org/W4291017752","doi":"https://doi.org/10.3389/fonc.2022.915862","title":"Investigational cyclin-dependent kinase 4/6 inhibitor GLR2007 demonstrates activity against isocitrate dehydrogenase wild-type glioblastoma and other solid tumors in mice xenograft models","display_name":"Investigational cyclin-dependent kinase 4/6 inhibitor GLR2007 demonstrates activity against isocitrate dehydrogenase wild-type glioblastoma and other solid tumors in mice xenograft models","publication_year":2022,"publication_date":"2022-08-11","ids":{"openalex":"https://openalex.org/W4291017752","doi":"https://doi.org/10.3389/fonc.2022.915862","pmid":"https://pubmed.ncbi.nlm.nih.gov/36033522","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/9403987"},"language":"en","primary_location":{"id":"doi:10.3389/fonc.2022.915862","doi":"https://doi.org/10.3389/fonc.2022.915862","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fonc.2022.915862","pdf_url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.915862/pdf","source":{"id":"https://openalex.org/S2596394214","display_name":"Frontiers in Oncology","issn_l":"2234-943X","issn":["2234-943X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Oncology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.915862/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5101528173","display_name":"Lei Yin","orcid":"https://orcid.org/0000-0003-4795-8710","observed_orcids":["https://orcid.org/0000-0003-4795-8710"]},"institutions":[{"id":"https://openalex.org/I4210142553","display_name":"Lee's Pharmaceutical (China)","ror":"https://ror.org/04abccf14","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210142553"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Lei Yin","raw_affiliation_strings":["Gan & Lee Pharmaceuticals, Beijing, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Gan & Lee Pharmaceuticals, Beijing, China","institution_ids":["https://openalex.org/I4210142553"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110930640","display_name":"Zhenglin Yao","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210142553","display_name":"Lee's Pharmaceutical (China)","ror":"https://ror.org/04abccf14","country_code":"CN","type":"company","lineage":["https://openalex.org/I4210142553"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhenglin Yao","raw_affiliation_strings":["Gan & Lee Pharmaceuticals, Beijing, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Gan & Lee Pharmaceuticals, Beijing, China","institution_ids":["https://openalex.org/I4210142553"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100372139","display_name":"Yue Wang","orcid":"https://orcid.org/0009-0002-8013-780X","observed_orcids":["https://orcid.org/0009-0002-8013-780X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yue Wang","raw_affiliation_strings":["Gan & Lee Pharmaceuticals USA Corp., Bridgewater, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Gan & Lee Pharmaceuticals USA Corp., Bridgewater, NJ, United States","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5006606104","display_name":"Michelle Mazuranic","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michelle Mazuranic","raw_affiliation_strings":["Gan & Lee Pharmaceuticals USA Corp., Bridgewater, NJ, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Gan & Lee Pharmaceuticals USA Corp., Bridgewater, NJ, United States","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5101528173"],"corresponding_institution_ids":["https://openalex.org/I4210142553"],"apc_list":{"value":2950,"currency":"USD","value_usd":2950},"apc_paid":{"value":2950,"currency":"USD","value_usd":2950},"fwci":0.2244,"has_fulltext":true,"cited_by_count":4,"citation_normalized_percentile":{"value":0.44948263,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":96},"biblio":{"volume":"12","issue":null,"first_page":"915862","last_page":"915862"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.5410000085830688,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.5410000085830688,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T12829","display_name":"Advanced Breast Cancer Therapies","score":0.3345000147819519,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.02239999920129776,"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/cdk4-6-inhibitors","display_name":"CDK4/6 inhibitors","score":0.9350000023841858},{"id":"https://openalex.org/keywords/cdk4","display_name":"CDK4","score":0.8500000238418579},{"id":"https://openalex.org/keywords/cdk6","display_name":"CDK6","score":0.9980000257492065},{"id":"https://openalex.org/keywords/blood-brain-barrier-penetration","display_name":"blood-brain barrier penetration","score":0.9700000286102295},{"id":"https://openalex.org/keywords/brain-tumor-drug-delivery","display_name":"brain tumor drug delivery","score":0.5419999957084656},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":0.7080000042915344},{"id":"https://openalex.org/keywords/colorectal-cancer","display_name":"colorectal cancer","score":0.8389999866485596},{"id":"https://openalex.org/keywords/lung-cancer","display_name":"lung cancer","score":0.9769999980926514},{"id":"https://openalex.org/keywords/liver-cancer","display_name":"liver cancer","score":0.9700000286102295},{"id":"https://openalex.org/keywords/tumor-growth-inhibition","display_name":"tumor growth inhibition","score":0.8619999885559082},{"id":"https://openalex.org/keywords/abemaciclib","display_name":"abemaciclib","score":0.7179999947547913},{"id":"https://openalex.org/keywords/radiolabeled-drug-distribution","display_name":"radiolabeled drug distribution","score":0.6299999952316284},{"id":"https://openalex.org/keywords/cell-cycle-regulation","display_name":"cell cycle regulation","score":0.3610000014305115}],"concepts":[{"id":"https://openalex.org/C2777150147","wikidata":"https://www.wikidata.org/wiki/Q261968","display_name":"Isocitrate dehydrogenase","level":3,"score":0.722822904586792},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6209350228309631},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5314746499061584},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.5027952194213867},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.442476749420166},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.43419092893600464},{"id":"https://openalex.org/C2779744173","wikidata":"https://www.wikidata.org/wiki/Q15269707","display_name":"Palbociclib","level":5,"score":0.42678138613700867},{"id":"https://openalex.org/C199649820","wikidata":"https://www.wikidata.org/wiki/Q14911762","display_name":"Cyclin-dependent kinase 6","level":5,"score":0.4264848828315735},{"id":"https://openalex.org/C199835354","wikidata":"https://www.wikidata.org/wiki/Q15311861","display_name":"Cyclin D1","level":4,"score":0.4160216450691223},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.37623316049575806},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3536904454231262},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.26375287771224976},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.24286788702011108},{"id":"https://openalex.org/C2775930923","wikidata":"https://www.wikidata.org/wiki/Q12859063","display_name":"Metastatic breast cancer","level":4,"score":0.11493173241615295},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.11196291446685791},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.3389/fonc.2022.915862","doi":"https://doi.org/10.3389/fonc.2022.915862","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fonc.2022.915862","pdf_url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.915862/pdf","source":{"id":"https://openalex.org/S2596394214","display_name":"Frontiers in Oncology","issn_l":"2234-943X","issn":["2234-943X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Oncology","raw_type":"journal-article"},{"id":"pmid:36033522","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/36033522","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":"Frontiers in oncology","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:9403987","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9403987/","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Front Oncol","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:f181ab9d2f944ff7b4efa9fd4861ee7e","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/f181ab9d2f944ff7b4efa9fd4861ee7e","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":"Frontiers in Oncology, Vol 12 (2022)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fonc.2022.915862","doi":"https://doi.org/10.3389/fonc.2022.915862","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fonc.2022.915862","pdf_url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.915862/pdf","source":{"id":"https://openalex.org/S2596394214","display_name":"Frontiers in Oncology","issn_l":"2234-943X","issn":["2234-943X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Oncology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9907000064849854,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4291017752.pdf","grobid_xml":"https://content.openalex.org/works/W4291017752.grobid-xml"},"referenced_works_count":26,"referenced_works":["https://openalex.org/W1922104457","https://openalex.org/W2007988355","https://openalex.org/W2089353165","https://openalex.org/W2096287682","https://openalex.org/W2109816625","https://openalex.org/W2148977460","https://openalex.org/W2157005154","https://openalex.org/W2256833355","https://openalex.org/W2318725321","https://openalex.org/W2402797587","https://openalex.org/W2610403529","https://openalex.org/W2750328162","https://openalex.org/W2774173192","https://openalex.org/W2905067827","https://openalex.org/W2909018550","https://openalex.org/W2913928134","https://openalex.org/W2944448327","https://openalex.org/W2968318393","https://openalex.org/W2975525011","https://openalex.org/W3006710845","https://openalex.org/W3015696786","https://openalex.org/W3020099303","https://openalex.org/W3028371813","https://openalex.org/W3081949673","https://openalex.org/W3101726066","https://openalex.org/W4211220688"],"related_works":["https://openalex.org/W3167626185","https://openalex.org/W3215663832","https://openalex.org/W2774173192","https://openalex.org/W3203665213","https://openalex.org/W2157005154","https://openalex.org/W3006710845","https://openalex.org/W2955852147","https://openalex.org/W4416141060","https://openalex.org/W4393093894","https://openalex.org/W3111146433"],"abstract_inverted_index":{"Cyclin-dependent":[0],"kinases,":[1],"CDK4":[2],"and":[3,72,107,114,118,154,218,237],"CDK6,":[4],"are":[5],"essential":[6],"in":[7,15,33,48,81,89,104,121,141,167,174,204,213,224],"regulating":[8],"the":[9,57,70,84,168,246],"cell":[10,128,160],"cycle,":[11],"which":[12],"is":[13,51],"disrupted":[14],"cancers":[16],"like":[17],"isocitrate":[18],"dehydrogenase":[19],"wild-type":[20],"glioblastoma":[21],"(GBM).":[22],"Currently":[23],"marketed":[24],"CDK4/6":[25,54,75,243],"inhibitors,":[26],"including":[27,251],"abemaciclib,":[28],"have":[29],"shown":[30],"preclinical":[31],"efficacy":[32,47,99],"solid":[34,249],"tumors,":[35,250],"but":[36],"factors":[37],"such":[38],"as":[39,241],"poor":[40],"blood\u2013brain":[41],"barrier":[42],"(BBB)":[43],"penetration":[44,234],"limit":[45],"their":[46],"GBM.":[49,252],"GLR2007":[50,88,101,132,166,194,236],"an":[52],"investigational":[53],"inhibitor":[55,244],"with":[56,189],"potential":[58,240],"for":[59,245],"improved":[60],"BBB":[61,233],"penetration.":[62],"In":[63,126],"vitro":[64],"assays":[65],"were":[66],"used":[67],"to":[68],"assess":[69],"potency":[71],"inhibition":[73,199],"of":[74,78,86,100,143,147,151,156,164,170,235,248],"enzymatic":[76],"activity":[77],"GLR2007.":[79],"Using":[80],"vivo":[82],"assays,":[83,131],"distribution":[85],"radiolabeled":[87,165],"rats":[90,171],"was":[91,102],"determined":[92],"through":[93],"quantitative":[94],"whole-body":[95],"autoradiography.":[96],"The":[97],"antitumor":[98],"evaluated":[103],"human":[105,115],"GBM":[106,205],"breast":[108,214],"cancer":[109,120,159,215,226],"orthotopic":[110,206,216],"mice":[111],"xenograft":[112,124,184],"models,":[113],"lung,":[116,153],"colorectal,":[117],"liver":[119,158],"a":[122,242],"subcutaneous":[123,227],"model.":[125],"tumor":[127,197],"line":[129],"proliferation":[130,134],"inhibited":[133],"at":[135],"lower":[136],"concentration":[137],"values":[138],"than":[139],"abemaciclib":[140],"19":[142],"20":[144,150],"GBM,":[145],"five":[146],"seven":[148],"breast,":[149],"21":[152],"24":[155,157],"lines.":[161],"Total":[162],"levels":[163],"brains":[169],"exceeded":[172],"those":[173],"plasma":[175],"by":[176],"2.3\u20134.5-fold":[177],"from":[178],"2\u20136":[179],"hours":[180],"after":[181],"dosing.":[182],"A":[183],"model":[185],"showed":[186],"that,":[187],"compared":[188],"vehicle":[190],"control,":[191],"50":[192],"mg/kg":[193],"induced":[195],"95.9%":[196],"growth":[198],"(TGI)":[200],"(":[201,210,221],"P":[202,211,222],"<0.001)":[203,223],"xenografts,":[207,217],"81.4%":[208],"TGI":[209,220],"=0.037)":[212],"91.5%":[219],"colorectal":[225],"xenografts.":[228],"These":[229],"studies":[230],"show":[231],"possible":[232],"demonstrate":[238],"its":[239],"treatment":[247]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":1}],"updated_date":"2026-11-10T11:39:43.021295","created_date":"2022-08-13T00:00:00"}
