Diagenode

Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells


Tumber A. et al.

Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe2+-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of <100 nM for KDM5A-D in vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of ∼50 μM and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.

Tags
Antibody

Share this article

Published
March, 2017

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410003-50
    H3K4me3 polyclonal antibody - Premium

Events

  • Japanese Biochemical Society
    Yokohama
    Sep 18-Sep 20, 2019
  • The 2019 PacBio Long-Read Revolution: Highly Accurate and Affordable SMRT Sequencing
    Atlanta, Georgia
    Sep 19, 2019
  • The 2019 PacBio Long-Read Revolution: Highly Accurate and Affordable SMRT Sequencing
    RTP, North Carolina
    Sep 20, 2019
  • EpiGeneSys
    London
    Sep 22-Sep 24, 2019
 See all events

         Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics