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

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 9010319 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4812 (Electronic) Linking ISSN: 10431802 NLM ISO Abbreviation: Bioconjug Chem Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Chemical Society, c1990-
    • Subject Terms:
      DNA*/chemistry ; Indazoles*/chemistry ; Indazoles*/pharmacology ; E1A-Associated p300 Protein*/antagonists & inhibitors ; E1A-Associated p300 Protein*/metabolism ; Small Molecule Libraries*/chemistry ; Small Molecule Libraries*/pharmacology ; Drug Discovery*/methods; Humans ; Gene Library ; Ligands
    • 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.
    • Accession Number:
      9007-49-2 (DNA)
      0 (Indazoles)
      EC 2.3.1.48 (E1A-Associated p300 Protein)
      0 (Small Molecule Libraries)
      EC 2.3.1.48 (EP300 protein, human)
      0 (Ligands)
    • Publication Date:
      Date Created: 20240808 Date Completed: 20240821 Latest Revision: 20241101
    • Publication Date:
      20241102
    • Accession Number:
      10.1021/acs.bioconjchem.4c00307
    • Accession Number:
      39116103