{"created":"2023-07-27T06:38:32.260273+00:00","id":26636,"links":{},"metadata":{"_buckets":{"deposit":"b85d5cad-bad7-41fd-9530-14970991186f"},"_deposit":{"created_by":3,"id":"26636","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"26636"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00026636","sets":["1761:1762:1763"]},"author_link":["44735","22059","44736","44738","44737","44734","44733"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2008-01-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"5","bibliographicPageEnd":"687","bibliographicPageStart":"682","bibliographicVolumeNumber":"56","bibliographic_titles":[{"bibliographic_title":"Chemical and Pharmaceutical Bulletin"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-β receptor (PDGFβ R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFβ R-ligand interactions, is urgently needed. Here we present models of the PDGFβ R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by α-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFβ R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors. © 2008 Pharmaceutical Society of Japan.","subitem_description_type":"Abstract"}]},"item_4_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学附属病院薬剤部","subitem_description_type":"Other"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"日本薬学会"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1248/cpb.56.682","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA00602100","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0009-2363","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Mori, Yoshikazu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hirokawa, Takatsugu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Aoki, Katsuyuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Satomi, Hisanori"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takeda, Shuichi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Aburada, Masaki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Miyamoto, Ken-ichi"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-05"}],"displaytype":"detail","filename":"HO-PR-MIYAMOTO-K-982.pdf","filesize":[{"value":"2.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"HO-PR-MIYAMOTO-K-982.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/26636/files/HO-PR-MIYAMOTO-K-982.pdf"},"version_id":"1a99543c-cdbe-4863-a2bb-f3bce44c304f"}]},"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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Structure Activity Relationships of Quinoxalin-2-one Derivatives as Platelet-Derived Growth Factor-β Receptor (PDGFβ R) Inhibitors, Derived from Molecular Modeling","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Structure Activity Relationships of Quinoxalin-2-one Derivatives as Platelet-Derived Growth Factor-β Receptor (PDGFβ R) Inhibitors, Derived from Molecular Modeling"}]},"item_type_id":"4","owner":"3","path":["1763"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-05"},"publish_date":"2017-10-05","publish_status":"0","recid":"26636","relation_version_is_last":true,"title":["Structure Activity Relationships of Quinoxalin-2-one Derivatives as Platelet-Derived Growth Factor-β Receptor (PDGFβ R) Inhibitors, Derived from Molecular Modeling"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-27T21:21:18.202205+00:00"}