Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep 1;26(17):4350-4.
doi: 10.1016/j.bmcl.2016.07.026. Epub 2016 Jul 19.

Identification of potent, selective KDM5 inhibitors

Victor S Gehling  1 , Steven F Bellon  2 , Jean-Christophe Harmange  2 , Yves LeBlanc  2 , Florence Poy  2 , Shobu Odate  2 , Shane Buker  2 , Fei Lan  2 , Shilpi Arora  2 , Kaylyn E Williamson  2 , Peter Sandy  2 , Richard T Cummings  2 , Christopher M Bailey  2 , Louise Bergeron  2 , Weifeng Mao  3 , Amy Gustafson  4 , Yichin Liu  4 , Erica VanderPorten  4 , James E Audia  2 , Patrick Trojer  2 , Brian K Albrecht  2
Affiliations

Identification of potent, selective KDM5 inhibitors

Victor S Gehling et al. Bioorg Med Chem Lett. .

Abstract

This communication describes the identification and optimization of a series of pan-KDM5 inhibitors derived from compound 1, a hit initially identified against KDM4C. Compound 1 was optimized to afford compound 20, a 10nM inhibitor of KDM5A. Compound 20 is highly selective for the KDM5 enzymes versus other histone lysine demethylases and demonstrates activity in a cellular assay measuring the increase in global histone 3 lysine 4 tri-methylation (H3K4me3). In addition compound 20 has good ADME properties, excellent mouse PK, and is a suitable starting point for further optimization.

Keywords: Epigenetics; Histone lysine demethylase; JARID1; KDM5.

PubMed Disclaimer

Substances

LinkOut - more resources