{"created":"2024-11-19T02:03:56.267662+00:00","id":2007994,"links":{},"metadata":{"_buckets":{"deposit":"6391c2a8-8ae3-435a-a4f2-e8deff491726"},"_deposit":{"created_by":48,"id":"2007994","owner":"48","owners":[48],"pid":{"revision_id":0,"type":"depid","value":"2007994"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02007994","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["1005","1415","1496","943","1307","521","670","228"],"control_number":"2007994","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"新規BCR-ABL1 アロステリック阻害剤アシミニブは薬剤耐性の有無に関わらずイマチニブとの併用で相乗効果を示す","subitem_alternative_title_language":"ja"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2024-06-21","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageStart":"e1214","bibliographicVolumeNumber":"12","bibliographic_titles":[{"bibliographic_title":"Pharmacology Research & Perspectives","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"In the treatment of chronic myeloid leukemia (CML), resistance to BCR-ABL inhibitors makes it difficult to continue treatment and is directly related to life expectancy. Therefore, asciminib was introduced to the market as a useful drug for overcoming drug resistance. While combining molecular targeted drugs is useful to avoid drug resistance, the new BCR-ABL inhibitor asciminib and conventional BCR-ABL inhibitors should be used as monotherapy in principle. Therefore, we investigated the synergistic effect and mechanism of the combination of asciminib and imatinib. We generated imatinib-resistant cells using the human CML cell line K562, examined the effects of imatinib and asciminib exposure on cell survival using the WST-8 assay, and comprehensively analyzed genetic variation related to drug resistance using RNA-seq and real-time PCR. A synergistic effect was observed when imatinib and asciminib were combined with or without imatinib resistance. Three genes, GRRP1, ESPN, and NOXA1, were extracted as the sites of action of asciminib. Asciminib in combination with BCR-ABL inhibitors may improve the therapeutic efficacy of conventional BCR-ABL inhibitors and prevent the development of resistance. Its dosage may be effective even at minimal doses that do not cause side effects. Further verification of this mechanism of action is needed. Additionally, cross-resistance between BCR-ABL inhibitors and asciminib may occur, which needs to be clarified through further validation as soon as possible.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"British Pharmacological Society","subitem_publisher_language":"en"},{"subitem_publisher":"American Society for Pharmacology and Experimental Therapeutics","subitem_publisher_language":"en"},{"subitem_publisher":"John Wiley & Sons"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"20521707","subitem_source_identifier_type":"EISSN"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3845号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2024-09-12"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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徳島大学大学院医学研究科（医学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1616号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1002/prp2.1214"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1002/prp2.1214","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"415119"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"岡本, 尚大","creatorNameLang":"ja"},{"creatorName":"オカモト, ナオキ","creatorNameLang":"ja-Kana"},{"creatorName":"Okamoto, 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leukemia","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Asciminib","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"BCR-ABL inhibitors","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Drug Resistance","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Asciminib, a novel allosteric inhibitor of BCR-ABL1, shows synergistic effects when used in combination with imatinib with or without drug resistance","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Asciminib, a novel allosteric inhibitor of BCR-ABL1, shows synergistic effects when used in combination with imatinib with or without drug resistance","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"48","path":["1716268551628"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-12-09"},"publish_date":"2024-12-09","publish_status":"0","recid":"2007994","relation_version_is_last":true,"title":["Asciminib, a novel allosteric inhibitor of BCR-ABL1, shows synergistic effects when used in combination with imatinib with or without drug resistance"],"weko_creator_id":"48","weko_shared_id":-1},"updated":"2025-01-31T01:49:43.230591+00:00"}