{"id":"https://openalex.org/W1998135606","doi":"https://doi.org/10.1158/1535-7163.targ-13-a275","title":"Abstract A275: Co-targeting PIM and PI3K/mTOR pathways with a single molecule: Novel orally available combined PIM/PI3K and PIM/PI3K/mTOR kinase inhibitors.","display_name":"Abstract A275: Co-targeting PIM and PI3K/mTOR pathways with a single molecule: Novel orally available combined PIM/PI3K and PIM/PI3K/mTOR kinase inhibitors.","publication_year":2013,"publication_date":"2013-11-01","ids":{"openalex":"https://openalex.org/W1998135606","doi":"https://doi.org/10.1158/1535-7163.targ-13-a275","mag":"1998135606"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.targ-13-a275","doi":"https://doi.org/10.1158/1535-7163.targ-13-a275","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.targ-13-a275","pdf_url":null,"source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Therapeutics","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5029217625","display_name":"Carmen Blanco\u2010Aparicio","orcid":"https://orcid.org/0000-0002-3249-6595","observed_orcids":["https://orcid.org/0000-0002-3249-6595"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Carmen Blanco Aparicio","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025774025","display_name":"Oliver Renner","orcid":"https://orcid.org/0000-0002-4046-0517","observed_orcids":["https://orcid.org/0000-0002-4046-0517"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Oliver Renner","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010605692","display_name":"Elena G\u00f3mez\u2010Casero","orcid":"https://orcid.org/0000-0002-7040-8832","observed_orcids":["https://orcid.org/0000-0002-7040-8832"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Elena Gomez-Casero","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019156368","display_name":"Antonio Cebri\u00e1","orcid":"https://orcid.org/0000-0001-8222-0848","observed_orcids":["https://orcid.org/0000-0001-8222-0848"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Antonio Cebri\u00e1","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045034656","display_name":"Nuria Ajenjo","orcid":"https://orcid.org/0000-0002-9435-6467","observed_orcids":["https://orcid.org/0000-0002-9435-6467"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Nuria Ajenjo","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066130407","display_name":"Enara Aguirre","orcid":"https://orcid.org/0000-0002-0188-3533","observed_orcids":["https://orcid.org/0000-0002-0188-3533"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Enara Aguirre","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043187017","display_name":"David\u00a0\u00c1lvaro Cebri\u00e1n","orcid":"https://orcid.org/0009-0006-5793-4172","observed_orcids":["https://orcid.org/0009-0006-5793-4172"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"David Cebri\u00e1n","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042961343","display_name":"Ma Carmen Rodriguez de Miguel","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"M\u00aa Carmen Rodriguez de Miguel","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090488385","display_name":"Bel\u00e9n Peque\u00f1o","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Bel\u00e9n Peque\u00f1o","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109108726","display_name":"MaIsabel Albarr\u00e1n","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"M\u00aaIsabel Albarr\u00e1n","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081617809","display_name":"Rosario Concepcion Riesco","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Rosario Riesco","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010709756","display_name":"Ana Bel\u00e9n Garc\u00eda","orcid":"https://orcid.org/0000-0003-2510-2049","observed_orcids":["https://orcid.org/0000-0003-2510-2049"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Ana Bel\u00e9n Garc\u00eda","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101914374","display_name":"Rosa M. \u00c1lvarez","orcid":"https://orcid.org/0000-0002-4692-559X","observed_orcids":["https://orcid.org/0000-0002-4692-559X"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Rosa Alvarez","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112373459","display_name":"Michael F. O\u2018Neill","orcid":"https://orcid.org/0000-0001-8253-4329","observed_orcids":["https://orcid.org/0000-0001-8253-4329"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael O'Neill","raw_affiliation_strings":["2Inflection Bioscience, Dublin, Ireland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Inflection Bioscience, Dublin, Ireland","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060108499","display_name":"Sonia Mart\u00ednez","orcid":"https://orcid.org/0000-0003-2230-7794","observed_orcids":["https://orcid.org/0000-0003-2230-7794"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Sonia Martinez","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5088584202","display_name":"Joaqu\u00edn Pastor","orcid":"https://orcid.org/0000-0003-0553-8021","observed_orcids":["https://orcid.org/0000-0003-0553-8021"]},"institutions":[{"id":"https://openalex.org/I4210089594","display_name":"Spanish National Cancer Research Centre","ror":"https://ror.org/00bvhmc43","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4210089594"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Joaquin Pastor","raw_affiliation_strings":["1Spanish National Cancer Research Centre (CNIO), Madrid, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Spanish National Cancer Research Centre (CNIO), Madrid, Spain","institution_ids":["https://openalex.org/I4210089594"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"12","issue":"11_Supplement","first_page":"A275","last_page":"A275"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":1.0,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":1.0,"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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.0,"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/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.0,"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/pim-kinases","display_name":"PIM kinases","score":0.9210000038146973},{"id":"https://openalex.org/keywords/pi3k-mtor-inhibitors","display_name":"PI3K/mTOR inhibitors","score":0.7009999752044678},{"id":"https://openalex.org/keywords/pi3k-akt-mtor-pathway","display_name":"PI3K/AKT/mTOR pathway","score":0.8669999837875366},{"id":"https://openalex.org/keywords/dual-kinase-inhibitors","display_name":"dual kinase inhibitors","score":0.7179999947547913},{"id":"https://openalex.org/keywords/gdc-0941","display_name":"GDC-0941","score":0.8029999732971191},{"id":"https://openalex.org/keywords/rapamycin-resistance","display_name":"rapamycin resistance","score":0.7360000014305115},{"id":"https://openalex.org/keywords/compensatory-signaling","display_name":"compensatory signaling","score":0.7260000109672546},{"id":"https://openalex.org/keywords/lymphoma","display_name":"lymphoma","score":0.492000013589859},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.8379999995231628},{"id":"https://openalex.org/keywords/oral-bioavailability","display_name":"oral bioavailability","score":0.37599998712539673}],"concepts":[{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.9426474571228027},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.7857714295387268},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.6240205764770508},{"id":"https://openalex.org/C107846503","wikidata":"https://www.wikidata.org/wiki/Q14876061","display_name":"mTORC2","level":5,"score":0.5707858204841614},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.49069273471832275},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.4854141175746918},{"id":"https://openalex.org/C43060935","wikidata":"https://www.wikidata.org/wiki/Q18043110","display_name":"RPTOR","level":4,"score":0.46894025802612305},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4423619508743286},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4395185112953186},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.41599828004837036},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.38374078273773193},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.282505601644516}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1535-7163.targ-13-a275","doi":"https://doi.org/10.1158/1535-7163.targ-13-a275","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1535-7163.targ-13-a275","pdf_url":null,"source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Therapeutics","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.98580002784729,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2082551177","https://openalex.org/W2407410863","https://openalex.org/W1982401280","https://openalex.org/W1980300780","https://openalex.org/W2909481138","https://openalex.org/W2102148658","https://openalex.org/W4243125471","https://openalex.org/W7098128843","https://openalex.org/W2115021142","https://openalex.org/W7097397193"],"abstract_inverted_index":{"Abstract":[0],"The":[1,37,144],"PI3K/AKT":[2],"pathway":[3],"is":[4,28,61,94,103],"commonly":[5],"activated":[6,150],"in":[7,84,141,159,164,188,191,200,216,228,258,359,382,396,398,425,470],"human":[8],"cancer.":[9],"Multiple":[10],"small-molecule":[11],"inhibitors":[12,140,282,288,349,375,392,432],"have":[13,169,205,232,302,310,387,393,410,433],"been":[14,303,394,434],"developed":[15],"to":[16,50,52,72,89,105,118,126,134,153,208,323,345,380],"target":[17],"PI3K/mTOR":[18,129,524],"or":[19,337],"AKT":[20,73,93,127],"kinases,":[21,66],"but":[22,99],"the":[23,31,136,173,206,223,254,446,452,463,543],"efficacy":[24,137,212,424],"of":[25,33,39,57,114,138,175,197,225,238,261,297,369,414,440,458,542],"these":[26],"drugs":[27],"compromised":[29],"by":[30,64,92,97],"stimulation":[32],"compensatory":[34,59],"signaling":[35,41],"pathways.":[36],"redundancy":[38],"oncogenic":[40,70],"pathways":[42,60,148,525],"provides":[43],"back-up":[44],"mechanisms":[45],"that":[46,62,172],"allow":[47],"cancer":[48,405],"cells":[49,117,343],"escape":[51],"targeted":[53,419],"therapies.":[54],"One":[55],"example":[56],"such":[58,198],"driven":[63],"PIM":[65,100,122,147,181,336,522],"which":[67,318],"produce":[68],"parallel":[69],"signals":[71],"and":[74,76,128,131,146,151,163,213,243,257,265,279,286,315,325,347,356,361,365,373,386,402,421,460,462,472,523,535,549],"mTOR":[75],"share":[77],"several":[78],"downstream":[79],"molecular":[80],"targets.":[81],"In":[82,249],"fact,":[83],"mouse":[85,406],"lymphoma":[86],"models":[87,427],"chemoresistance":[88],"doxorubicin":[90],"caused":[91],"readily":[95],"reversed":[96],"rapamycin,":[98],"mediated":[101],"resistance":[102,113,125,215],"refractory":[104],"mTORC1":[106],"inhibition.":[107],"Moreover,":[108],"PIM2":[109],"kinase":[110,291,537],"can":[111],"confer":[112],"primary":[115],"hematopoietic":[116],"rapamycin":[119],"treatment.":[120],"Furthermore,":[121],"1":[123],"mediates":[124],"inhibition":[130,327],"suggests":[132],"co-targeting":[133],"improve":[135],"PI3K/AKT/mTOR":[139,145,220],"anticancer":[142],"therapy.":[143],"are":[149,274,376],"seem":[152],"be":[154],"relevant":[155],"for":[156,305,454,465],"tumor":[157],"progression":[158],"many":[160],"lymphomas,":[161],"leukemias":[162],"some":[165],"solid":[166],"tumors.":[167,474],"We":[168,309],"previously":[170],"reported":[171],"combination":[174,196],"PI3K":[176,338],"inhibitor":[177],"GDC-0941":[178],"with":[179,218,240,328,350,378,417,437,526],"a":[180,201,234,295,320,351,466,527],"selective":[182,339],"inhibitor,":[183],"ETP-45299,":[184],"was":[185],"strongly":[186],"synergistic":[187],"antiproliferation":[189],"experiments":[190],"MV-4-11":[192],"AML":[193,360,471],"cells.":[194],"Therefore,":[195],"activities":[199],"single":[202,528],"molecule":[203],"might":[204],"potential":[207,467],"achieve":[209],"better":[210],"clinical":[211,468],"prevent/suppress":[214],"comparison":[217],"classical":[219],"inhibitors.":[221,269,341,538],"During":[222],"course":[224],"our":[226],"investigations":[227],"this":[229,250],"field":[230],"we":[231,252],"identified":[233,311],"new":[235],"chemical":[236],"series":[237],"compounds":[239,273,301,409],"dual":[241,262,285,324,346,372],"(PIM/PI3K)":[242],"triple":[244,266,287,326,348,374],"activity":[245],"(PIM/PI3K/mTOR":[246],"inhibitors).":[247],"(WO2012/156756).":[248],"work,":[251],"show":[253,289],"biochemical,":[255],"cellular":[256],"vivo":[259,397],"characterization":[260],"PIM/PI3K":[263,278,534],"ETP-539/(IBL-202)":[264],"PIM/PI3K/mTOR":[267,281,536],"ETP-339/(IBL-301)":[268,461],"These":[270,284,391,431,449],"optimized":[271,377],"lead":[272],"low":[275],"nanomolar":[276],"pan":[277,280],"respectively.":[283],"excellent":[290,388],"selectivity":[292],"profile":[293,420],"against":[294],"panel":[296],"456":[298],"kinases.":[299],"Both":[300,408],"profiled":[304],"their":[306,381,418],"antiproliferative":[307],"behavior.":[308],"leukemia,":[312],"lymphoma,":[313],"colon,":[314],"NSCLC":[316,362,473],"lines":[317],"exhibit":[319],"strong":[321,366],"sensitivity":[322],"GI80":[329],"between":[330],"5-10":[331],"times":[332,444],"more":[333],"potent":[334],"than":[335],"reference":[340],"Mechanistically,":[342],"respond":[344],"clear":[352],"cell":[353,363],"cycle":[354],"arrest":[355],"marked":[357],"apoptosis":[358],"lines,":[364],"down":[367,412],"regulation":[368,413],"biomarkers.":[370],"Our":[371],"respect":[379],"vitro":[383],"ADME":[384],"properties":[385],"oral":[389,429],"bioavailability.":[390],"tested":[395],"xenograft":[399],"(MV4:11":[400],"AML)":[401],"transgenic":[403],"(KRAsV12NSCLC)":[404],"models.":[407],"demonstrated":[411],"biomarkers":[415],"associated":[416],"significant":[422],"antitumor":[423],"both":[426],"after":[428],"administration.":[430],"well":[435],"tolerated,":[436],"no":[438],"signs":[439],"toxicity":[441],"even":[442],"20":[443],"above":[445],"efficacious":[447],"dose.":[448],"results":[450],"provide":[451],"rationale":[453],"further":[455],"preclinical":[456],"development":[457],"ETP-539/(IBL-202":[459],"basis":[464],"use":[469],"Citation":[475,482],"Information:":[476],"Mol":[477,560],"Cancer":[478,550,561],"Ther":[479,562],"2013;12(11":[480,563],"Suppl):A275.":[481],"Format:":[483],"Carmen":[484,500],"Blanco":[485],"Aparicio,":[486],"Oliver":[487],"Renner,":[488],"Elena":[489],"Gomez-Casero,":[490],"Antonio":[491],"Cebri\u00e1,":[492],"Nuria":[493],"Ajenjo,":[494],"Enara":[495],"Aguirre,":[496],"David":[497],"Cebri\u00e1n,":[498],"Ma":[499],"Rodriguez":[501],"de":[502],"Miguel,":[503],"Bel\u00e9n":[504,511],"Peque\u00f1o,":[505],"MaIsabel":[506],"Albarr\u00e1n,":[507],"Rosario":[508],"Riesco,":[509],"Ana":[510],"Garc\u00eda,":[512],"Rosa":[513],"Alvarez,":[514],"Michael":[515],"O'Neill,":[516],"Sonia":[517],"Martinez,":[518],"Joaquin":[519],"Pastor.":[520],"Co-targeting":[521],"molecule:":[529],"Novel":[530],"orally":[531],"available":[532],"combined":[533],"[abstract].":[539],"In:":[540],"Proceedings":[541],"AACR-NCI-EORTC":[544],"International":[545],"Conference:":[546],"Molecular":[547],"Targets":[548],"Therapeutics;":[551],"2013":[552],"Oct":[553],"19-23;":[554],"Boston,":[555],"MA.":[556],"Philadelphia":[557],"(PA):":[558],"AACR;":[559],"Suppl):Abstract":[564],"nr":[565],"A275.":[566]},"counts_by_year":[{"year":2016,"cited_by_count":1},{"year":2014,"cited_by_count":1}],"updated_date":"2026-11-10T11:39:43.021295","created_date":"2016-06-24T00:00:00"}
