2. Academic Validation
  3. Discovery Small-Molecule p300 Inhibitors Derived from a Newly Developed Indazolone-Focused DNA-Encoded Library

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

  • Bioconjug Chem. 2024 Aug 21;35(8):1251-1257. doi: 10.1021/acs.bioconjchem.4c00307.
Yanrui Suo 1 2,  Kaige Li 3,  Xing Ling 1 2,  Kenian Yan 1 2,  Weiwei Lu 1,  Jinfeng Yue 1,  Xiaohua Chen 1 2,  Zhiqiang Duan 1,  Xiaojie Lu 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
  • 2 University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
  • 3 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road ,Nanjing 210023, China.
PMID: 39116103 DOI: 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.

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