Yanrui Suo; Kaige Li; Xing Ling; Kenian Yan; Weiwei Lu; Jinfeng Yue; Xiaohua Chen; Zhiqiang Duan; Xiaojie Lu
Bioconjugate Chem., 2024, XXXX, XXX, XXX-XXX
https://doi.org/10.1021/acs.bioconjchem.4c00307

Abstract

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.