5-(3-(N-(Carboxymethyl)naphthalene-2-sulfonamido)phenyl)-1-ethyl-1H-pyrrole-2-carboxylic acid as a Keap1–Nrf2 inhibitor for cerebral ischemia/reperfusion injury treatment

Abstract

The Keap1 (Kelch-like ECH-Associating Protein 1)–Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2)-ARE (Antioxidant Response Element) signaling pathway plays a crucial role in the oxidative stress response and has been linked to the development and progression of various diseases. Its influence on cerebral ischemia/reperfusion (I/R) injury has garnered significant attention. In our study, we investigated the effect of compound 2, a non-covalent inhibitor of the Keap1–Nrf2 interaction, which was previously discovered by our research group. Specifically, we used 5-(3-(N-(carboxymethyl)naphthalene-2-sulfonamido)phenyl)-1-ethyl-1H-pyrrole-2-carboxylic acid (compound 2) to assess its therapeutic potential in a cerebral I/R injury model. The results demonstrated that compound 2 had a significant therapeutic effect, promoting the translocation of Nrf2 from the cytoplasm to the nucleus in diseased tissue. Additionally, it increased the production of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH).