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Small Molecule Inhibitors of KDM5 histone demethylases
Yale University
Small molecule
Oncology
Hit To Lead or Lead Optimization
• KDM5A/B histone demethylases are amplified and overexpression in multiple solid tumors, making these enzymes ideal targets for cancer therapy
• KDM5B loss/inhibition induced robust antitumor immune response, leading to prolong survival of tumor bearing mice in multiple models (Figure below)
• Specific inhibitors of KDM5 inhibitors (IC50s of ~20 nM) have been identified. 35 high-resolution crystal structures (1.22-2.29 Å) of KDM5A with various inhibitors are available to support further medicinal chemistry optimization
US 2019-0151289 A1