KSS72

KSS72 is a novel, non-diuretic, brain-penetrating small molecule analog of ethacrynic acid (EA) designed for the treatment of glioblastoma (GBM). Developed by researchers at Texas Tech University Health Sciences Center, KSS72 addresses the poor blood-brain barrier (BBB) permeability of its parent compound by removing the carboxylate side chain, resulting in a more hydrophobic molecule. It functions by inhibiting glutathione S-transferase pi (GSTpi) and depleting cellular antioxidants, including glutathione (GSH) and NADPH. This depletion leads to a significant increase in reactive oxygen species (ROS), triggering endoplasmic reticulum (ER) stress, MAPK activation, autophagy, and apoptosis in glioma cells. In preclinical orthotopic GBM models, KSS72 demonstrated potent antitumor efficacy and complete elimination of intracranial tumors without significant systemic toxicity.

Other names

1-(2,3-dichloro-4-methoxyphenyl)-2-methylenebutan-1-one