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Issue 2, 2017
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Small molecules inhibiting Keap1–Nrf2 protein–protein interactions: a novel approach to activate Nrf2 function

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Abstract

Oxidative stress is well recognized to contribute to the cause of a wide range of diseases, such as cancer, diabetes, Alzheimer's disease, arteriosclerosis, and inflammation. The Keap1–Nrf2–ARE pathway plays a critical regulatory role and can protect cells from oxidative stress through activating Nrf2 to induce its downstream phase II enzymes. Nrf2 activation through the covalent inactivation of Keap1 may cause unpredictable side effects. Non-covalent disruption of the Keap1–Nrf2 protein–protein interactions is an alternative strategy for Nrf2 activation, potentially with reduced risk of toxicity. Efforts have been made in recent years to develop peptide- and small molecule-based Keap1–Nrf2 PPI inhibitors via different approaches, including high-throughput screening, target-based virtual screening, structure-based optimization, and fragment-based drug design. This review aims to highlight the recently discovered small-molecule inhibitors as well as their therapeutic potential.

Graphical abstract: Small molecules inhibiting Keap1–Nrf2 protein–protein interactions: a novel approach to activate Nrf2 function

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Publication details

The article was received on 01 Sep 2016, accepted on 16 Nov 2016 and first published on 17 Nov 2016


Article type: Review Article
DOI: 10.1039/C6MD00500D
Citation: Med. Chem. Commun., 2017,8, 286-294
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    Small molecules inhibiting Keap1–Nrf2 protein–protein interactions: a novel approach to activate Nrf2 function

    C. Zhuang, Z. Wu, C. Xing and Z. Miao, Med. Chem. Commun., 2017, 8, 286
    DOI: 10.1039/C6MD00500D

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