AL1311 is a highly potent NRF2 activator that is being developed for Autosomal Dominant Polycystic Kidney disease (ADPKD). AL1311 is different from other electrophilic and reactive NRF2 activators because it works by disrupting the protein-protein interaction between NRF2 and its regulatory protein Keap1. Non-reactive NRF2 activators have the potential to have better specificity for NRF2 activation and therefore a better safety profile.  

Activation of NRF2 has been shown to reduce the oxidative stress and inflammation that are critical to ADPKD pathogenesis.  Consequentially, NRF2 activators have been shown to slow cyst growth and preserve kidney function in ADPKD animal models.

Lu Y, Sun Y, Liu Z, Lu Y, Zhu X, Lan B, Mi Z, Dang L, Li N, Zhan W, Tan L, Pi J, Xiong H, Zhang L, Chen Y. Activation of NRF2 ameliorates oxidative stress and cystogenesis in autosomal dominant polycystic kidney disease. Sci Transl Med. 2020 Jul 29;12(554):eaba3613. doi: 10.1126/scitranslmed.aba3613. PMID: 32727915.