RA839

RA839 is an inhibitor of the protein-protein interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2).¹ It binds non-covalently to the Keap1 Kelch domain (K_d = ^~6 µM). RA839 increases Nrf2-dependent transcription driven by antioxidant response element (ARE) in a reporter assay using HepG2 cells and induces Nrf2 nuclear translocation in U2OS cells (EC₅₀ = 1.2 µM). It reduces LPS-induced increases in nitric oxide (NO) in bone marrow-derived macrophages (BMDMs) when used at concentrations ranging from 5 to 20 µM. RA839 (20 µM) reduces the levels of rotavirus structural proteins in infected MA-104 cells, an effect that is partially blocked by Nrf2 shRNA.² It also decreases propagation of the rotavirus strains SA11, Wa, and A5-13 in MA-104 cells (IC₅₀s = 10.303, 6.187, and 11.97 µM, respectively) and reduces viral titers in infected HT-29 and HEK293 cells (IC₅₀s = 11.815 and 9.686 µM, respectively).

WARNING This product is not for human or veterinary use.

1. Winkel, A.F., Engel, C.K., Margerie, D., et al. Characterization of RA839, a noncovalent small molecule binder to Keap1 and selective activator of Nrf2 signaling. The Journal of Biological Chemisty 290(47), 27446-28455 (2015).

2. Patra, U., Mukhopadhyay, U., Sarkar, R., et al. RA-839, a selective agonist of Nrf2/ARE pathway, exerts potent anti-rotaviral efficacy in vitro. Antiviral Res. 161, 53-62 (2019).