PST-001

PST-001 is a potent, highly selective, and orally active small molecule inhibitor of Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), developed by Pharmasum Therapeutics. Built upon a 5-methoxybenzothiazole scaffold and optimized with an acetamidopyridine moiety, the compound is designed to penetrate the blood-brain barrier and target the ATP-binding pocket of the DYRK kinase family. PST-001 demonstrates high selectivity (GINI-index of 0.936), effectively inhibiting DYRK1A, DYRK2, DYRK3, and CLK2 while sparing GSK3β. In preclinical models of Alzheimer's disease and Down syndrome, PST-001 has been shown to reduce the pathological hyperphosphorylation of Tau protein at the Serine 262 site, ameliorate neurodegeneration, and rescue deficits in memory, locomotor performance, and sleep patterns.