1083407-66-2Relevant academic research and scientific papers
HISTONE LYSINE DEMETHYLASE INHIBITORS
-
Page/Page column 73; 76, (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.
Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases
Rose, Nathan R.,Ng, Stanley S.,Mecinovi?, Jasmin,Liénard, Beno?t M. R.,Bello, Simon H.,Sun, Zhe,McDonough, Michael A.,Oppermann, Udo,Schofield, Christopher J.
supporting information; experimental part, p. 7053 - 7056 (2009/11/30)
The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze the physiological roles of these enzymes in epigenetic signaling.
