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Multiple targets have been addressed for NASH therapy reflecting the complex pathophysiology of this disease. CureDiab has identified thioacrylamidederivatives (HK1,3,4) that mediate allosteric activation of peripheral GABA-A receptors, resulting in a prominent hepatoprotection and an anti-fibrotic response. Pre-clinical studies were conducted using hepatocytes under lipotoxic conditions, activated human stellate cells and a mouse model of fibrosis. The preventive effect of HK was demonstrated by reduced caspase 3/7 activity in HepG2 and primary human hepatocyte.
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