19-phenyl-17-DMAG

19-phenyl DMAG (also known as 19-phenyl-17-DMAG or 19Ph-DMAG) is a novel 19-substituted benzoquinone ansamycin (BQA) derivative designed as an inhibitor of heat shock protein 90 (Hsp90) with reduced hepatotoxicity. Developed by researchers at the University of Colorado and the University of Nottingham, the compound was engineered to prevent the off-target toxicities associated with parent BQAs like 17-DMAG. Specifically, the 19-phenyl substitution prevents glutathione conjugation and nonspecific interactions with protein thiols (arylation of cellular nucleophiles), which are major drivers of BQA-induced hepatotoxicity. 19-phenyl DMAG acts as an Hsp90 inhibitor in a NAD(P)H:quinone oxidoreductase 1 (NQO1)-dependent manner, where NQO1 reduces the quinone to a more active hydroquinone form that stably binds the ATP-binding site of Hsp90. This leads to the degradation of Hsp90 client proteins (such as Raf-1, Akt, and HER2) and compensatory induction of Hsp70, resulting in growth inhibition and apoptosis in breast cancer cells.

Other names

19-phenyl DMAG19-phenyl-17-DMAG19Ph-DMAG