Pharmacology and Clinical Drug Candidates in Redox Medicine

V. Thao-Vi Dao, Ana I. Casas, Ghassan J. Maghzal, Tamara Seredenina, Nina Kaludercic, Natalia Robledinos-Anton, Fabio Di Lisa, Roland Stocker, Pietro Ghezzi, Vincent Jaquet, Antonio Cuadrado and Harald H.H.W. Schmidt; Antioxid Redox Signal. 2015 November 10; 23(14): 1113–1129. doi: 10.1089/ars.2015.6430

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Other lines of research have focused on targeting NRF2 in degenerative diseases where low-grade chronic inflammation is present. One very potent synthetic triterpenoid, CDDO-methyl ester, bardoxolone methyl, has been studied in great detail for treatment of diabetic nephropathy. The initial excitement about this compound was set back by a small yet significant increase in the risk of heart failure. Importantly though, this effect appears not to be related to NRF2 targeting, but rather to alteration of endothelin signaling, leading to reduction in urine volume and sodium excretion in some patients with advanced chronic kidney disease. Bardoxolone methyl is now being studied in new indications for pulmonary arterial hypertension, melanoma, and Friedreich's ataxia.


 Pharmacology and Clinical Drug Candidates in Redox Medicine