Discovery Small-Molecule p300 Inhibitors Derived from a Newly Developed Indazolone-Focused DNA-Encoded Library

The DNA-encoded library (DEL) is a robust tool for chemical
biology
and drug discovery. In this study, we developed a DNA-compatible light-promoted
reaction that is highly efficient and plate-compatible for DEL construction
based on the formation of the indazolone scaffold. Employing this
high-efficiency approach, we constructed a DEL featuring an indazolone
core, which enabled the identification of a novel series of ligands
specifically targeting E1A-binding protein (p300) after DEL selection.
Taken together, our findings underscore the feasibility of light-promoted
reactions in DEL synthesis and unveil promising avenues for developing
p300-targeting inhibitors.