Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates.
Based on structural analysis of the human 2-oxoglutarate (2OG) dependent JMJD2 histone N(ε)-methyl lysyl demethylase family, 3-substituted pyridine 2,4-dicarboxylic acids were identified as potential inhibitors with possible selectivity over other human 2OG oxygenases. Microwave-assisted palladium-c...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1797050445314654208 |
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| author | Thalhammer, A Mecinović, J Loenarz, C Tumber, A Rose, N Heightman, T Schofield, C |
| author_facet | Thalhammer, A Mecinović, J Loenarz, C Tumber, A Rose, N Heightman, T Schofield, C |
| author_sort | Thalhammer, A |
| collection | OXFORD |
| description | Based on structural analysis of the human 2-oxoglutarate (2OG) dependent JMJD2 histone N(ε)-methyl lysyl demethylase family, 3-substituted pyridine 2,4-dicarboxylic acids were identified as potential inhibitors with possible selectivity over other human 2OG oxygenases. Microwave-assisted palladium-catalysed cross coupling methodology was developed to install a diverse set of substituents on the sterically demanding C-3 position of a pyridine 2,4-dicarboxylate scaffold. The subsequently prepared di-acids were tested for in vitro inhibition of the histone demethylase JMJD2E and another human 2OG oxygenase, prolyl-hydroxylase domain isoform 2 (PHD2, EGLN1). A subset of substitution patterns yielded inhibitors with selectivity for JMJD2E over PHD2, demonstrating that structure-based inhibitor design can enable selective inhibition of histone demethylases over related human 2OG oxygenases. |
| first_indexed | 2024-03-06T18:05:15Z |
| format | Journal article |
| id | oxford-uuid:013a9b0a-b83c-4b5f-8365-e752f827d850 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:05:15Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:013a9b0a-b83c-4b5f-8365-e752f827d8502022-03-26T08:33:42ZInhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:013a9b0a-b83c-4b5f-8365-e752f827d850EnglishSymplectic Elements at Oxford2011Thalhammer, AMecinović, JLoenarz, CTumber, ARose, NHeightman, TSchofield, CBased on structural analysis of the human 2-oxoglutarate (2OG) dependent JMJD2 histone N(ε)-methyl lysyl demethylase family, 3-substituted pyridine 2,4-dicarboxylic acids were identified as potential inhibitors with possible selectivity over other human 2OG oxygenases. Microwave-assisted palladium-catalysed cross coupling methodology was developed to install a diverse set of substituents on the sterically demanding C-3 position of a pyridine 2,4-dicarboxylate scaffold. The subsequently prepared di-acids were tested for in vitro inhibition of the histone demethylase JMJD2E and another human 2OG oxygenase, prolyl-hydroxylase domain isoform 2 (PHD2, EGLN1). A subset of substitution patterns yielded inhibitors with selectivity for JMJD2E over PHD2, demonstrating that structure-based inhibitor design can enable selective inhibition of histone demethylases over related human 2OG oxygenases. |
| spellingShingle | Thalhammer, A Mecinović, J Loenarz, C Tumber, A Rose, N Heightman, T Schofield, C Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. |
| title | Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. |
| title_full | Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. |
| title_fullStr | Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. |
| title_full_unstemmed | Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. |
| title_short | Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. |
| title_sort | inhibition of the histone demethylase jmjd2e by 3 substituted pyridine 2 4 dicarboxylates |
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