{"@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/1360004234764895232.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1093/toxsci/kfr086"}},{"identifier":{"@type":"URI","@value":"http://academic.oup.com/toxsci/article-pdf/122/1/157/16683095/kfr086.pdf"}},{"identifier":{"@type":"PMID","@value":"21505091"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Fluorothalidomide: A Characterization of Maternal and Developmental Toxicity in Rabbits and Mice"}],"description":[{"notation":[{"@value":"The expanding therapeutic uses of thalidomide (TD) are limited by its teratogenic side effects. Although the therapeutic and teratogenic effects may be stereoselectively separable, rapid in vivo racemization of the TD isomers confounds the corroboration of this distinction. Herein we evaluated the potential of fluorothalidomide (FTD), the closest structural analog of TD with stable, nonracemizing isomers, as a model compound for studying stereoselectivity in TD teratogenesis. In contrast to TD, FTD was a potent maternal and fetal toxicant in both rabbits and mice in vivo. Furthermore, FTD rapidly degraded in vivo, presumably via hydrolysis, which in vitro was up to 22-fold faster for FTD than TD. Most critically, in an established rabbit embryo culture model for TD teratogenesis, FTD did not initiate the limb bud embryopathies observed with TD. The chemical instability and strikingly different maternal and developmental toxicological profiles of FTD and TD make FTD an unsuitable compound for studying stereoselective mechanisms of TD teratogenesis."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004234764895235","@type":"Researcher","foaf:name":[{"@value":"Crystal J. J. Lee"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751139382656","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"40293302"},{"@type":"NRID","@value":"1000040293302"},{"@type":"NRID","@value":"9000403595999"},{"@type":"NRID","@value":"9000318134974"},{"@type":"NRID","@value":"9000254706184"},{"@type":"NRID","@value":"9000402014470"},{"@type":"NRID","@value":"9000406560003"},{"@type":"NRID","@value":"9000411023085"},{"@type":"NRID","@value":"9000411564783"},{"@type":"NRID","@value":"9000016657218"},{"@type":"NRID","@value":"9000005218519"},{"@type":"NRID","@value":"9000005162824"},{"@type":"NRID","@value":"9000005183653"},{"@type":"NRID","@value":"9000403596895"},{"@type":"NRID","@value":"9000403596661"},{"@type":"NRID","@value":"9000345347481"},{"@type":"NRID","@value":"9000257722717"},{"@type":"NRID","@value":"9000016581923"},{"@type":"NRID","@value":"9000254700033"},{"@type":"NRID","@value":"9000242708700"},{"@type":"NRID","@value":"9000005162404"},{"@type":"NRID","@value":"9000403595741"},{"@type":"NRID","@value":"9000403597089"},{"@type":"NRID","@value":"9000402006354"},{"@type":"NRID","@value":"9000018232852"},{"@type":"NRID","@value":"9000005198550"},{"@type":"NRID","@value":"9000021043644"},{"@type":"NRID","@value":"9000254705287"},{"@type":"NRID","@value":"9000254715242"},{"@type":"NRID","@value":"9000412664921"},{"@type":"NRID","@value":"9000403596948"},{"@type":"NRID","@value":"9000399261596"},{"@type":"NRID","@value":"9000254703064"},{"@type":"NRID","@value":"9000401805486"},{"@type":"NRID","@value":"9000017113622"},{"@type":"NRID","@value":"9000345430074"},{"@type":"NRID","@value":"9000403595234"},{"@type":"NRID","@value":"9000254241888"},{"@type":"NRID","@value":"9000257730218"},{"@type":"NRID","@value":"9000254705662"},{"@type":"NRID","@value":"9000401678346"},{"@type":"NRID","@value":"9000403594819"},{"@type":"NRID","@value":"9000242086843"},{"@type":"NRID","@value":"9000408634713"},{"@type":"NRID","@value":"9000020321464"},{"@type":"NRID","@value":"9000403595905"},{"@type":"NRID","@value":"9000391612851"},{"@type":"NRID","@value":"9000403596890"},{"@type":"NRID","@value":"9000403597240"},{"@type":"NRID","@value":"9000254240435"},{"@type":"NRID","@value":"9000403595227"},{"@type":"NRID","@value":"9000257732179"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/nozshiba"}],"foaf:name":[{"@value":"Norio Shibata"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234764895233","@type":"Researcher","foaf:name":[{"@value":"Michael J. Wiley"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234764895232","@type":"Researcher","foaf:name":[{"@value":"Peter G. Wells"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"10966080"},{"@type":"EISSN","@value":"10960929"}],"prism:publicationName":[{"@value":"Toxicological Sciences"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2011-04-19","prism:volume":"122","prism:number":"1","prism:startingPage":"157","prism:endingPage":"169"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"http://academic.oup.com/toxsci/article-pdf/122/1/157/16683095/kfr086.pdf"}],"createdAt":"2011-04-20","modifiedAt":"2025-03-05","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Dose-Response%20Relationship,%20Drug","dc:title":"Dose-Response Relationship, Drug"},{"@id":"https://cir.nii.ac.jp/all?q=Limb%20Buds","dc:title":"Limb Buds"},{"@id":"https://cir.nii.ac.jp/all?q=Hydrolysis","dc:title":"Hydrolysis"},{"@id":"https://cir.nii.ac.jp/all?q=Abnormalities,%20Drug-Induced","dc:title":"Abnormalities, Drug-Induced"},{"@id":"https://cir.nii.ac.jp/all?q=Pilot%20Projects","dc:title":"Pilot Projects"},{"@id":"https://cir.nii.ac.jp/all?q=Embryo,%20Mammalian","dc:title":"Embryo, Mammalian"},{"@id":"https://cir.nii.ac.jp/all?q=Thalidomide","dc:title":"Thalidomide"},{"@id":"https://cir.nii.ac.jp/all?q=Embryo%20Culture%20Techniques","dc:title":"Embryo Culture Techniques"},{"@id":"https://cir.nii.ac.jp/all?q=Fetal%20Diseases","dc:title":"Fetal Diseases"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Teratogens","dc:title":"Teratogens"},{"@id":"https://cir.nii.ac.jp/all?q=Pregnancy","dc:title":"Pregnancy"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=Rabbits","dc:title":"Rabbits"},{"@id":"https://cir.nii.ac.jp/all?q=Chromatography,%20High%20Pressure%20Liquid","dc:title":"Chromatography, High Pressure Liquid"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782101733760","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22106515"},{"@type":"JGN","@value":"JP22106515"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY-22106515/"}],"notation":[{"@language":"ja","@value":"含フッ素生理活性物質の集積合成"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282257049451136","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"21390030"},{"@type":"JGN","@value":"JP21390030"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390030/"}],"notation":[{"@language":"ja","@value":"フッ素薬学:官能基導入に力点を置いた創薬"},{"@language":"en","@value":"Fluorinated Medicines : Drug Development based on Functional Groups"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011144683637120","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Metabolism of Fluorine-Containing 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.ALPHA.-Methyl-N(.ALPHA.)-phthalimidoglutarimide, but Not Its (R)-Form, Enhanced Phorbol Ester-Induced Tumor Necrosis Factor-.ALPHA. Production by Human Leukemia Cell HL-60: Implication of Optical Resolution of Thalidomidal Effects."},{"@value":"(S)-form of alpha-methyl-N(alpha)-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-alpha production in human leukemia cell HL-60: implication of optical resolution of thalidomide effects"},{"@value":"(S)-form of alpha-methyl-N (alpha)-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-alpha production by human leukemia cell HL-60"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679141234944","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Tumor Necrosis Factor-Alpha Production Enhancing Activity of Substituted 3'-Methylthalidomide: Influence of Substituents at the Phthaloyl Moiety on the Activity and Stereoselectivity."},{"@value":"Tumor Necrosis Factor-Alpha Production Enhancing Activity of Substituted 3′-Methylthalidomide:Influence of Substituents at the Phthaloyl Moiety on the Activity and Stereoselectivity"},{"@language":"ja-Kana","@value":"Tumor Necrosis Factor-Alpha Production"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1093/toxsci/kfr086"},{"@type":"KAKEN","@value":"PRODUCT-13160940"},{"@type":"KAKEN","@value":"PRODUCT-12707719"},{"@type":"OPENAIRE","@value":"doi_dedup___::ebb470e9b61a74f122b721b158f20ad2"},{"@type":"CROSSREF","@value":"10.1039/c7sc05138g_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1039/c4sc03047h_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1002/chir.22683_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1038/s41598-018-35457-6_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1371/journal.pone.0182152_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1246/bcsj.20160223_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1021/acs.cgd.3c01030_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"},{"@type":"CROSSREF","@value":"10.1002/tcr.202300096_references_DOI_Bzy9a1gfWckstHKL1UKG2jxhgTj"}]}