The Keap1 –Nrf2 protein–protein interaction: A suitable target for small molecules

Publication date: Available online 31 October 2017 Source:Drug Discovery Today: Technologies Author(s): Dieter Schmoll, Christian K. Engel, Heiner Glombik The transcription factor Nrf2 controls pathways involved in oxidative-stress defense and is a potential pharmacological target for the treatment of chronic diseases. Activators of Nrf2 that have undergone clinical development are reactive molecules that are either associated with safety issues or for which it is unclear if their pharmacological efficacy depends on the activation of Nrf2. Therefore, the clinical validity of Nrf2 activation is not yet proven. The activity of Nrf2 is inhibited by Keap1 via a protein–protein interaction. Its structural characteristics allowed the identification of reversible small-molecule inhibitors of the Keap1–Nrf2 interaction that can hopefully elucidate the therapeutic potential of Nrf2 activation.

Source: Drug Discovery Today: Technologies - November 10, 2017 Category: Drugs & Pharmacology Source Type: research