Uniprot ID: O95931
Target SubClass: Methyl-lysine reader
Potency Value: 97 nM
Potency Assay: Isothermal titration calorimetry (ITC)
PDB ID for probe-target interaction (3D structure):
Detailed SAR data are available in a J. Med. Chem. publication that should be available shortly. SAR data were determined using an AlphaScreen assay, which is a bead-based competition assay that utilizes His-tagged proteins and biotinylated-peptide bait ligands. The SAR study primarily explored ligand length, unnatural methyl-lysine mimetics, and N-terminal modifications, as well as modifications to the phenylalanine side chain, alanine side chain, and C terminus. We found that certain tertiary amine mimetics of trimethyl-lysine are able to maintain similar affinities for chromodomains as Kme3 and Kme3 derivatives are not active in cells. A thorough examination of the N terminus of our inhibitors has also begun to establish the requirements for optimizing potency and selectivity for the Pc, HP1 and CDY families of chromodomains. CBX4/7 show a strong preference for alkyl substituents located at the para-position of the N-terminal benzoyl cap.
Chromobox protein homolog 7, CBX7, CBX7_HUMAN