Patent Review (2017–2020) of the Keap1/Nrf2 Pathway Using PatSeer Pro: Focus on Autoimmune Diseases

Introduction

Nuclear factor erythroid 2-related factor 2 (Nrf2, encoded by Nfe2l2/NFE2L2) is a transcription factor that coordinates the cellular responses to oxidative, electrophilic, and nitrosative stresses. Kelch-like ECH-associated protein 1 (Keap1) is a cysteine-rich protein that facilitates the rapid proteasomal degradation of Nrf2 under basal conditions. Upon exposure to reactive oxygen species, other stressors, or various natural and synthetic Nrf2-activating compounds, the sulfhydryl groups of Keap1 cysteines are modified, leading to allosteric modification of Keap1 that renders it unable to target Nrf2 for degradation. Thus, de novo transcribed and translated Nrf2 accumulates in the cell and enters the nucleus, where it recognizes specific sequences called antioxidant response elements (AREs) in the regulating regions of its target genes

Abstract

Research on the antioxidant pathway comprising the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) is ever increasing. As modulators of this pathway have started to be used in clinical trials and clinical practice, Nrf2 has become the subject of several patents. To assess the patent landscape of the last three years on Nrf2 and evaluate the main fields they refer to, we used the web-based tool PatSeer Pro to identify patents mentioning the Nrf2 pathway between January 2017 and May 2020

This search resulted in 509 unique patents that focus on topics such as autoimmune, neurodegenerative, liver, kidney, and lung diseases and refer to modulators (mainly activators) of the Nrf2 pathway as potential treatments. Autoimmunity emerged as the main theme among the topics of Nrf2 patents, including a broad range of diseases, such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, Hashimoto’s thyroiditis, etc.

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