Discovery\nSmall-Molecule p300 Inhibitors Derived from\na Newly Developed Indazolone-Focused DNA-Encoded Library

The DNA-encoded library (DEL) is a robust tool for chemical\nbiology\nand drug discovery. In this study, we developed a DNA-compatible light-promoted\nreaction that is highly efficient and plate-compatible for DEL construction\nbased on the formation of the indazolone scaffold. Employing this\nhigh-efficiency approach, we constructed a DEL featuring an indazolone\ncore, which enabled the identification of a novel series of ligands\nspecifically targeting E1A-binding protein (p300) after DEL selection.\nTaken together, our findings underscore the feasibility of light-promoted\nreactions in DEL synthesis and unveil promising avenues for developing\np300-targeting inhibitors.