Bardoxolone methyl

Bardoxolone (CDDO; RTA 401) methyl is an orally active and brain-penetrant activator of Nrf2 and an inhibitor of SARS-CoV-2 3CL protease. Bardoxolone methyl inhibits SARS-CoV-2 replication in Vero cells with an EC₅₀ value of 0.29 μM. Bardoxolone methyl increases levels of pNrf2 and HO-1, inhibits inflammatory mediators like pNFκB and MCP-1. Bardoxolone methyl activates the Nrf2 pathway to enhance antioxidant and anti-inflammatory responses, inhibits viral replication, and improves mitochondrial function. Bardoxolone methyl can be used in research on chemotherapy-induced neuropathic pain (CINP), COVID-19, and chronic kidney disease (CKD)^{[1][2][3][4][5]}. IC50 & Target:Nrf2^[1] In Vitro:Bardoxolone methyl (5, 10 mg/kg) significantly decreases in levels of renal KIM-1, NGAL, TNF-α, TOS, OSI and improves deterioration in glomeruli and tubules similarly to NAC (HY-B0215) in rat kidney homogenates^[3].
Bardoxolone methyl (0.3 and 1 μM, 28 h) decreases PAC-induced mitochondrial damage in the dorsal root ganglia (DRG) neuronal cell lines and increases pNRf2 intensity in the PAC-treated DRG cells^[4].
In Vivo:Bardoxolone methyl (30 mg/kg, p.o.) decreases renal expression of megalin but not cubilin, increases creatinine clearance and urinary albumin-to-creatinine ratios, and induces Nrf2 cytoprotective targets in cynomolgus monkeys^[1].
Bardoxolone methyl induces overall favorable effects on the heart via its improvement in eGFR in both animal models and clinical trials^[2].
Bardoxolone methyl(5, 10 mg/kg) decreased the percentage of caspase-3 immunopositive cells in a dose-dependent manner in rat kidney ^[3].
Bardoxolone methyl (0-10 mg/kg, i.p., a single dose) results in analgesia but not sedation in rats^[4].
Bardoxolone methyl [10 mg/kg, twice-daily on day 21 after the first PAC (HY-B0015) injection] decreases PAC-induced levels of pNFκB and MCP-1 by increasing pNRf2 and HO-1 in rat DRG^[4].