ArticleRSC medicinal chemistry2026
Synthesis and structure-activity relationships of small-molecule 2-pyridone based CBX7 inhibitors.
Article in RSC medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
CBX7 plays an important role in the epigenetic regulation of aggressive malignancies. The discovery of small-molecule and drug-like inhibitors is key to studying this protein's biological function and in the development of therapeutics. Herein we report the campaign that led to the cell-active and potent CBX7 small-molecule inhibitor EC134. From an initial high throughput screen, a 2-pyridone compound class was identified and 30 structural analogs were made through a convergent synthetic route that allowed for easy diversification. Multiple regions of the scaffold were modified including the 2-pyridone, a piperazine core and a terminal aromatic group. An SAR was established identifying key substituents necessary for binding, and most intriguing was the positioning of methyl groups around a pyridine-aryl bond, showing a sharp line between potency and inactivity that we explored using molecular docking studies. This work resulted in four hit compounds with potent IC
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