Discovery and Characterization of a Cellular Potent Positive Allosteric Modulator of the Polycomb Repressive Complex 1 Chromodomain, CBX7 (Cell Chemical Biology)

Lamb et al. describe the discovery of UNC4976 as a cellularly efficacious inhibitor of CBX7. Despite similar potency, selectivity, and permeability to previously published probe UNC3866, UNC4976 possesses a unique mechanism of action as a positive allosteric modulator of nucleic acid binding to CBX7 that rationalizes its enhanced cellular activity.