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An updated patent review of Nrf2 activators (2020-present)

Ziquan Zhao1,2, Ruitian Dong1,2, Keni Cui1,2

  • 1State Key Laboratory of Natural Medicines, and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China.

Expert Opinion on Therapeutic Patents
|February 21, 2023
PubMed
Abstract

Insights

Activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway shows promise for treating oxidative stress-related diseases. Recent Nrf2 activators demonstrate efficacy, though challenges in target selectivity and brain permeability remain.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating cellular defense against oxidative stress.
  • The Kelch-like ECH-associated protein 1-Nrf2-antioxidant response element (Keap1-Nrf2-ARE) pathway is central to Nrf2 regulation.
  • Oxidative stress is implicated in various chronic diseases, making Nrf2 activation a therapeutic target.

Approach:

  • This review summarizes the biological effects and regulatory mechanisms of the Keap1-Nrf2-ARE pathway.
  • It details Nrf2 activators developed between 2020 and the present, categorized by their mechanism of action.
  • Case studies include chemical structures, biological activities, structural optimization, and clinical development of these activators.

Key Points:

  • Novel Nrf2 activators have been developed with enhanced potency and drug-like properties.
  • These compounds show therapeutic potential in preclinical models of oxidative stress-related diseases.
  • Ongoing research focuses on improving target selectivity and blood-brain barrier penetration.

Conclusions:

  • Nrf2 pathway activation is a viable therapeutic strategy for chronic diseases linked to oxidative stress.
  • Recent advancements in Nrf2 activator development show significant promise.
  • Future efforts should address challenges in specificity and CNS delivery for broader clinical application.
Keywords:
AREKeap1Nrf2 activatorschronic diseaseselectrophilic activatorsprotein–protein interaction inhibitors

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