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ID: ALA4219204
Journal: Bioorg Med Chem Lett
Title: Structure-based design and discovery of potent and selective KDM5 inhibitors.
Authors: Nie Z, Shi L, Lai C, O'Connell SM, Xu J, Stansfield RK, Hosfield DJ, Veal JM, Stafford JA.
Abstract: Histone lysine demethylases (KDMs) play a key role in epigenetic regulation and KDM5A and KDM5B have been identified as potential anti-cancer drug targets. Using structural information from known KDM4 and KDM5 inhibitors, a potent series of pyrazolylpyridines was designed. Structure-activity relationship (SAR) exploration resulted in the identification of compound 33, an orally available, potent inhibitor of KDM5A/5B with promising selectivity. Potent cellular inhibition as measured by levels of tri-methylated H3K4 was demonstrated with compound 33 in the breast cancer cell line ZR-75-1.
CiteXplore: 29627262