Methods and compositions for modulating P300/CBP activity

摘要

The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.

主权项

1. A method for treating breast cancer, ovarian cancer, or melanoma in a subject, comprising administering to a subject in need thereof an effective amount of a p300/CBP inhibitor having the structure ofwherein
the dotted line represents an optional bond, R1 is H, NO2, or unsubstituted C1-4 alkyl; R2 and R3 are independently H, CH3, or NO2; and R4 and R5 are independently H, NO2, SO3H, halogen, COOH, CONH2, COCH2NH2, COOCH3, COOC2H5 or unsubstituted C1-4 alkyl.