3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O'PROTAC

Chem Commun (Camb). 2022 Feb 15;58(14):2383-2386. doi: 10.1039/d1cc06525d.

Abstract

In this study, we identified 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O'PROTAC for degradation of the ERG transcription factor. This phthalic acid-based O'PROTAC presented an efficacy in degrading ERG comparable to those displayed by pomalidomide-based ERG O'PROTACs. Moreover, phthalic acid-being more chemically stable and economical than classical immunomodulatory drugs (IMiDs)-represents, as a ligand, a new alternative for the development of PROTACs, especially O'PROTACs.

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Molecular Structure
  • Phthalic Acids / chemistry
  • Phthalic Acids / pharmacology*
  • Proteolysis / drug effects
  • Structure-Activity Relationship
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • 3-aminophthalate
  • Ligands
  • Phthalic Acids
  • Transcription Factors
  • Ubiquitin-Protein Ligases