Development of Keap1-interactive small molecules that regulate Nrf2 transcriptional activity

There has been considerable progress recently in the discovery and development of Keap1-interactive compounds that enhance Nrf2 transcriptional activity. The compounds fall into two broad classes: electrophilic cysteine-reactive compounds and non-electrophilic Keap1-Nrf2 protein–protein interaction inhibitors. This short review highlights structures from both classes and discusses their development, biological properties, and the future prospects for developing therapeutic agents. Molecules of both types have potential applications in areas including inflammatory conditions, chronic neurodegenerative diseases and possibly cancer chemoprevention.