Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors

Area of Science:

• Biochemistry
• Pharmacology
• Medicinal Chemistry

Background:

• The Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway is crucial for regulating cellular oxidative stress.
• The interaction between Nrf2 and its primary regulator, Kelch-like ECH-Associating protein 1 (Keap1), is a key target for therapeutic intervention.
• Developing inhibitors of the Keap1-Nrf2 interaction is a promising approach for treating diseases associated with oxidative stress.

Purpose of the Study:

• To review recent advancements in the development of Keap1-Nrf2 inhibitors.
• To summarize the chemical structures and potencies of newly reported peptide and small molecule inhibitors.
• To discuss the pharmacological effects and potential therapeutic applications of these inhibitors.

Main Methods:

• Literature review of scientific publications and patents.
• Analysis of reported chemical structures of Keap1-Nrf2 inhibitors.
• Evaluation of pharmacological data and proposed therapeutic uses.

Main Results:

• Numerous novel peptide and small molecule inhibitors targeting the Keap1-Nrf2 interaction have been developed.
• Several compounds demonstrate high potency in preclinical studies.
• Diverse chemical scaffolds have been explored, leading to a range of inhibitor designs.

Conclusions:

• Inhibitors of the Keap1-Nrf2 interaction represent a viable therapeutic strategy for oxidative stress-related conditions.
• Continued research into novel chemical entities and their pharmacological profiles is warranted.
• Further investigation into the clinical translation of Keap1-Nrf2 inhibitors holds significant promise for future treatments.