SIG1012

SIG1012 is an orally active small-molecule modulator of protein phosphatase 2A (PP2A) being developed by Signum Biosciences for neurodegenerative disorders characterized by tau pathology, including Alzheimer’s disease and other tauopathies. Identified using a phosphatase-focused screening platform, the compound inhibits PP2A demethylation and blocks PP2A methylesterase activity, thereby increasing PP2A methylation and enzymatic activity in neurons, which in turn reduces pathologic tau phosphorylation and restores healthier protein phosphorylation homeostasis.[1][8][10][13] SIG1012, originally discovered as a bioactive constituent of coffee, has shown dose‑dependent reductions in phosphorylated tau in neuronal cell lines, lowered tau phosphorylation in rats, and delayed motor deficits with improved survival in a tauopathy mouse model, and preclinical data suggest a favorable safety and toxicology profile supporting its advancement toward formal development for Alzheimer’s disease, Parkinson’s disease, and related indications.[1][8][10][13][18][20]