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Updated: Oct 23, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

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Developments of CRBN-based PROTACs as potential therapeutic agents

Chao Wang1, Yujing Zhang2, Yudong Wu1

  • 1The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China.

European Journal of Medicinal Chemistry
|August 19, 2021
PubMed

Insights

Protease-targeted chimeras (PROTACs) harness the ubiquitin system for targeted protein degradation. This review focuses on Cereblon (CRBN)-based PROTACs, highlighting their broad therapeutic potential beyond cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Protease-targeted chimeras (PROTACs) represent an innovative therapeutic modality.
  • PROTACs function by recruiting E3 ubiquitin ligases to induce targeted protein degradation.
  • Heterobifunctional PROTACs comprise an E3 ligase ligand, a linker, and a target protein ligand.

Purpose of the Study:

  • To provide a comprehensive update on recent advancements in Cereblon (CRBN)-based PROTACs.
  • To review the therapeutic applications of CRBN-based PROTACs across various disease areas.
  • To discuss the future prospects and challenges associated with CRBN-based PROTAC technology.

Main Methods:

  • Literature review of CRBN-based PROTAC research.
  • Categorization of PROTACs by disease area and target class.
  • Systematic presentation of degradants, alphabetized by target.

Main Results:

  • Identification of various small-molecule PROTACs, including CRBN, VHL, IAPs, MDM2, DCAF15, DCAF16, and RNF114-based systems.
  • CRBN-based PROTACs (e.g., ARV-110, ARV-471) show significant therapeutic promise.
  • CRBN-based PROTACs have demonstrated efficacy in cancer, cardiovascular, immune, neurodegenerative, and infectious diseases.

Conclusions:

  • CRBN-based PROTACs are a rapidly advancing field with broad therapeutic applicability.
  • Continued research is crucial for overcoming potential challenges and realizing the full potential of PROTACs.
  • CRBN-based PROTACs offer a promising new avenue for disease treatment.
Keywords:
CRBNDegradationPROTACsPromising treatmentUbiquitination

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