{"@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/1360004235490977536.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1111/cbdd.12909"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcbdd.12909"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/cbdd.12909"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Identification and structure–activity relationship of purine derivatives as novel <scp>MTH</scp>1 inhibitors"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>The human mutT homolog‐1 (<jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1) protein prevents the incorporation of oxidized nucleotides such as 2‐<jats:styled-content style=\"fixed-case\">OH</jats:styled-content>‐<jats:styled-content style=\"fixed-case\">dATP</jats:styled-content> and 8‐oxo‐<jats:styled-content style=\"fixed-case\">dGTP</jats:styled-content> during <jats:styled-content style=\"fixed-case\">DNA</jats:styled-content> replication by hydrolyzing them into their corresponding monophosphates. It was found previously that cancer cells could tolerate oxidative stress due to this enzymatic activity of <jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1 and its inhibition could be a promising approach to treat several types of cancer. This finding has been challenged recently with increasing line of evidence suggesting that the cancer cell‐killing effects of <jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1 inhibitors may be related to their engagement of off‐targets. We have previously reported a few purine‐based <jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1 inhibitors that enabled us to elucidate the dispensability of <jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1 in cancer cell survival. Here, we provide a detailed process of the identification of purine‐based <jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1 inhibitors. Several new compounds with potency in the submicromolar range are disclosed. Furthermore, the structure–activity relationship and associated binding mode prediction using molecular docking have provided insights for the development of highly potent <jats:styled-content style=\"fixed-case\">MTH</jats:styled-content>1 inhibitors.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004235490977545","@type":"Researcher","foaf:name":[{"@value":"Ashutosh Kumar"}],"jpcoar:affiliationName":[{"@value":"Structural Bioinformatics Team RIKEN Center for Life Science Technologies Yokohama Kanagawa Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004235490977802","@type":"Researcher","foaf:name":[{"@value":"Tatsuro Kawamura"}],"jpcoar:affiliationName":[{"@value":"Chemical Biology Research Group RIKEN Center for Sustainable Resource Science Wako Saitama Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004235490977537","@type":"Researcher","foaf:name":[{"@value":"Makoto Kawatani"}],"jpcoar:affiliationName":[{"@value":"Chemical Biology Research Group RIKEN Center for Sustainable Resource Science Wako Saitama Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004235490977410","@type":"Researcher","foaf:name":[{"@value":"Hiroyuki Osada"}],"jpcoar:affiliationName":[{"@value":"Chemical Biology Research Group RIKEN Center for Sustainable Resource Science Wako Saitama Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004235490977668","@type":"Researcher","foaf:name":[{"@value":"Kam Y. 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