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Design, Synthesis and Characterization of Covalent KDM5 Inhibitors.

Our latest research published in Angewandte Chemie

Histone lysine demethylases (KDMs) are involved in the dynamic regulation of gene expression and they play a critical role in several biological processes. Achieving selectivity over the different KDMs has been a major challenge for KDM inhibitor development. Here we report potent and selective KDM5 covalent inhibitors designed to target cysteine residues only present in the KDM5 sub‐family. The covalent binding to the targeted proteins was confirmed by MS and time‐dependent inhibition. Additional competition assays show that compounds were non 2‐OG competitive. Target engagement and ChIP‐seq analysis showed that the compounds inhibited the KDM5 members in cells at nano‐ to micromolar levels and induce a global increase of the H3K4me3 mark at transcriptional start sites.

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Two open postdoc positions available!

We are looking for two enthusiastic postdoctoral fellows with expertise in structural biology to join us in our effort to study the function of proteins involved in #ubiquitination & #RNAmetabolism -

Open PostDoc position!

Great news: we have an open position for a PostDoc in structural biology/ biochemisrty. We would love to welcome you to our team, please apply here.


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