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Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine 2,4 dione family compounds SMI 16a and SMI 4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX 6258 and PIM447. SMI 16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations, and reduced in vitro colony forming capacity and in vivo tumorigenic activity in MM cells, suggesting impairment of their clonogenic capacity. PIM2 is known to be subject to ubiquitination-independent proteasomal degradation. Consistently, the proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in MM cells without affecting its mRNA levels. However, SMI 16a mitigated the PIM2 protein increase and cooperatively enhanced anti MM effects in combination with carfilzomib. Collectively, the thiazolidine 2,4 dione family compounds SMI 16a and SMI 4a uniquely reduce PIM2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Wiley","subitem_publisher_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"00071048","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"13652141","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AA00574570","subitem_source_identifier_type":"NCID"},{"subitem_source_identifier":"AA11618011","subitem_source_identifier_type":"NCID"}]},"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3206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":"2018-09-13"}]},"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 access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開\n本論文は, 著者Shiro Fujiiの学位論文として提出され, 学位審査・授与の対象となっている。\nThis is the peer reviewed version of the following article: Fujii, S. , Nakamura, S. , Oda, A. , Miki, H. , Tenshin, H. , Teramachi, J. , Hiasa, M. , Bat‐Erdene, A. , Maeda, Y. , Oura, M. , Takahashi, M. , Iwasa, M. , Endo, I. , Yoshida, S. , Aihara, K. , Kurahashi, K. , Harada, T. , Kagawa, K. , Nakao, M. , Sano, S. and Abe, M. (2018), Unique anti‐myeloma activity by thiazolidine‐2,4‐dione compounds with Pim inhibiting activity. Br J Haematol, 180: 246-258, which has been published in final form at https://doi.org/10.1111/bjh.15033. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.\n学位授与者所属 : 徳島大学大学院医科学教育部（プロテオミクス医科学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1380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":"10.1111/bjh.15033"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1111/bjh.15033","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"341053"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"藤井, 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