{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825895162573440.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/417254a"}},{"identifier":{"@type":"URI","@value":"http://www.nature.com/articles/417254a.pdf"}},{"identifier":{"@type":"URI","@value":"http://www.nature.com/articles/417254a"}},{"identifier":{"@type":"PMID","@value":"12015581"}},{"identifier":{"@type":"NAID","@value":"30013825861"}}],"dc:title":[{"@value":"Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis"}],"description":[{"notation":[{"@value":"The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1582543026270739712","@type":"Researcher","foaf:name":[{"@value":"M. B. Pepys"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573576","@type":"Researcher","foaf:name":[{"@value":"J. Herbert"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573568","@type":"Researcher","foaf:name":[{"@value":"W. L. Hutchinson"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573447","@type":"Researcher","foaf:name":[{"@value":"G. A. Tennent"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573448","@type":"Researcher","foaf:name":[{"@value":"H. J. Lachmann"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573569","@type":"Researcher","foaf:name":[{"@value":"J. R. Gallimore"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573444","@type":"Researcher","foaf:name":[{"@value":"L. B. Lovat"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573574","@type":"Researcher","foaf:name":[{"@value":"T. Bartfai"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573443","@type":"Researcher","foaf:name":[{"@value":"A. Alanine"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573571","@type":"Researcher","foaf:name":[{"@value":"C. Hertel"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573445","@type":"Researcher","foaf:name":[{"@value":"T. Hoffmann"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573451","@type":"Researcher","foaf:name":[{"@value":"R. Jakob-Roetne"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573575","@type":"Researcher","foaf:name":[{"@value":"R. D. Norcross"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573441","@type":"Researcher","foaf:name":[{"@value":"J. A. Kemp"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573572","@type":"Researcher","foaf:name":[{"@value":"K. Yamamura"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573577","@type":"Researcher","foaf:name":[{"@value":"M. Suzuki"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573446","@type":"Researcher","foaf:name":[{"@value":"G. W. Taylor"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573570","@type":"Researcher","foaf:name":[{"@value":"S. Murray"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573452","@type":"Researcher","foaf:name":[{"@value":"D. Thompson"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573440","@type":"Researcher","foaf:name":[{"@value":"A. Purvis"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573449","@type":"Researcher","foaf:name":[{"@value":"S. Kolstoe"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573450","@type":"Researcher","foaf:name":[{"@value":"S. P. Wood"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895162573442","@type":"Researcher","foaf:name":[{"@value":"P. N. Hawkins"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00280836"},{"@type":"EISSN","@value":"14764687"}],"prism:publicationName":[{"@value":"Nature"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2002-05","prism:volume":"417","prism:number":"6886","prism:startingPage":"254","prism:endingPage":"259"},"reviewed":"false","dc:rights":["http://www.springer.com/tdm"],"url":[{"@id":"http://www.nature.com/articles/417254a.pdf"},{"@id":"http://www.nature.com/articles/417254a"}],"createdAt":"2002-07-26","modifiedAt":"2023-05-18","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Models,%20Molecular","dc:title":"Models, Molecular"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Structure","dc:title":"Protein Structure"},{"@id":"https://cir.nii.ac.jp/all?q=Pyrrolidines","dc:title":"Pyrrolidines"},{"@id":"https://cir.nii.ac.jp/all?q=Carboxylic%20Acids","dc:title":"Carboxylic Acids"},{"@id":"https://cir.nii.ac.jp/all?q=Crystallography,%20X-Ray","dc:title":"Crystallography, X-Ray"},{"@id":"https://cir.nii.ac.jp/all?q=Quaternary","dc:title":"Quaternary"},{"@id":"https://cir.nii.ac.jp/all?q=Inhibitory%20Concentration%2050","dc:title":"Inhibitory Concentration 50"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Models","dc:title":"Models"},{"@id":"https://cir.nii.ac.jp/all?q=/dk/atira/pure/core/subjects/biomedicalsciences","dc:title":"/dk/atira/pure/core/subjects/biomedicalsciences"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Structure,%20Quaternary","dc:title":"Protein Structure, Quaternary"},{"@id":"https://cir.nii.ac.jp/all?q=Crystallography","dc:title":"Crystallography"},{"@id":"https://cir.nii.ac.jp/all?q=Molecular","dc:title":"Molecular"},{"@id":"https://cir.nii.ac.jp/all?q=Biomedical%20Sciences","dc:title":"Biomedical Sciences"},{"@id":"https://cir.nii.ac.jp/all?q=Amyloidosis","dc:title":"Amyloidosis"},{"@id":"https://cir.nii.ac.jp/all?q=Serum%20Amyloid%20P-Component","dc:title":"Serum Amyloid P-Component"},{"@id":"https://cir.nii.ac.jp/all?q=Cross-Linking%20Reagents","dc:title":"Cross-Linking Reagents"},{"@id":"https://cir.nii.ac.jp/all?q=Liver","dc:title":"Liver"},{"@id":"https://cir.nii.ac.jp/all?q=X-Ray","dc:title":"X-Ray"},{"@id":"https://cir.nii.ac.jp/all?q=Calcium","dc:title":"Calcium"},{"@id":"https://cir.nii.ac.jp/all?q=Dimerization","dc:title":"Dimerization"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Binding","dc:title":"Protein Binding"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285708512660352","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Multifaceted anti-amyloidogenic and pro-amyloidogenic effects of C-reactive protein and serum amyloid P component in vitro"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567182254320512","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Serum amyloid P component: A novel potential player in vessel degeneration in CADASIL"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567185412939136","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Proteomics Approach Identifies Factors Associated With the Response to Low‐Density Lipoprotein Apheresis Therapy in Patients With Steroid‐Resistant Nephrotic Syndrome"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848662450908288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Genetic Associations of Type 2 Diabetes with Islet Amyloid Polypeptide Processing and Degrading Pathways in Asian Populations"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865815507511168","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Bioprosthetic Valve Deterioration"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204263534592","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A Case of Salivary Gland Amyloidosis"},{"@value":"唾液腺アミロイドーシス例"},{"@language":"ja-Kana","@value":"リンショウ ダエキセン アミロイドーシスレイ"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679609169152","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Protective Effects of 4-Phenylbutyrate Derivatives on the Neuronal Cell Death and Endoplasmic Reticulum Stress"},{"@value":"Protective effects of - 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