257615-55-7Relevant academic research and scientific papers
Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates
Thalhammer, Armin,Mecinovic, Jasmin,Loenarz, Christoph,Tumber, Anthony,Rose, Nathan R.,Heightman, Tom D.,Schofield, Christopher J.
supporting information; experimental part, p. 127 - 135 (2011/02/24)
Based on structural analysis of the human 2-oxoglutarate (2OG) dependent JMJD2 histone Nε-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.
HISTONE LYSINE DEMETHYLASE INHIBITORS
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Page/Page column 94-95, (2010/04/30)
The invention provides a compound which is an iV-oxalylglycine derivative of formula (I): a hydroxamic acid derivative of formula (II): or a heteroaryl derivative of fomula (III): wherein n; Z1; Z2; Y1; Y2; A; p; X1; X2; m; R4; B; R5; R6; R7; R8; R9; X3; R10; R11 and R12 are as defined herein, or a pharmaceutically acceptable salt thereof. These compounds are inhibitors of the human 2-oxoglutarate-dependant JMJD2 subfamily of histone demethylases, in particular JMJD2E. Such inhibitors are useful in changing the epigenetic state of cells resulting in the inhibition / activation of chromatin remodelling, multiple gene activation / deactivation, and in treating cancer and other conditions characterised by undesirable cellular proliferation, and psychiatric disorders including depression.
Colubricidin A, a novel macrolide antibiotic from a Streptomyces sp.
Kong, Fangming,Liu, David Q.,Nietsche, Jeanne,Tischler, Mark,Carter, Guy T.
, p. 9219 - 9223 (2007/10/03)
A new 34-membered macrolide antibiotic, colubricidin A (1), was isolated from the fermentation broth of a new streptomyces species. Its structure was elucidated on the basis of analysis of the spectroscopic data and chemical degradation. It was identified as a glycomacrolide with an unprecedented aromatic chromophore. Colubricidin A showed excellent activity against Gram-positive bacteria.
