TLC-065

TLC-065 is a preclinical small molecule inhibitor of aminocarboxymuconate semialdehyde decarboxylase (ACMSD), developed for the treatment of metabolic and inflammatory liver and kidney diseases. ACMSD is a key enzyme in the de novo synthesis of NAD+, which is essential for mitochondrial function, redox state maintenance, sirtuin-mediated signaling, and energy homeostasis. In preclinical models, TLC-065 increases NAD+ levels, improves mitochondrial function, enhances fatty acid oxidation, and reduces lipogenesis, lipotoxicity, liver inflammation, and fibrosis. These effects have been demonstrated in mouse models of liver disease and in human liver organoids, where TLC-065 reduces DNA damage and disease markers. Its therapeutic rationale is based on restoring NAD+ levels to support metabolic health, DNA repair, and immune functions, with the potential to treat conditions like MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease), NASH (Nonalcoholic Steatohepatitis), and kidney diseases. The compound is being developed by OrsoBio, which acquired the ACMSD inhibitor program from Mitobridge, itself an Astellas company[1][3][4][7].

Other names

TLC-065TLC065TLC 065