mecripyrine (Y-1) / Simcere, Yantai YenePharma - LARVOL DELTA

Unprecedented polycyclic polyprenylated acylphloroglucinols with anti-Alzheimer's activity from St. John's wort. (PubMed, Chem Sci) - "Compounds 4 and 6 simultaneously displayed notable activation of PP2A (EC: 258.8 and 199.0 nM, respectively) and inhibition of BACE1 in cells (IC: 136.2 and 98.6 nM, respectively), and showed better activities than the positive controls SCR1693 (a PP2A activator, EC: 413.9 nM) and LY2811376 (a BACE1 inhibitor, IC: 260.2 nM). Furthermore, compound 6 showed better therapeutic effects with respect to the reduction of pathological and cognitive impairments in 3 × Tg AD mice than LY2811376. Compound 6 represents the first multitargeted natural product that could activate PP2A and simultaneously inhibit BACE1, which highlights compound 6 as a promising lead compound and a versatile scaffold in AD drug development."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

SCR-1693 inhibits tau phosphorylation and improves insulin resistance associated cognitive deficits. (PubMed, Neuropharmacology) - "Pre-treatment with the inhibitor of PP1 and PP2A inhibited the effect of SCR-1693 on both of tau phosphorylation and insulin signaling in Neura-2a-tau cells. All data suggest that an increase of activity of tau phosphatase was involved in the mechanism of SCR-1693 on the regulation of tau phosphorylation and insulin signaling, and SCR-1693 is considerable candidate for insulin resistance associated sporadic AD."

Journal

Tacrines as Therapeutic Agents for Alzheimer's Disease. IV. The Tacripyrines and Related Annulated Tacrines. (PubMed, Chem Rec) - "Notwithstanding the clinical use of tacrine was hampered by severe hepatotoxicity, tacrine still remains a reference scaffold in the search for new efficient drugs for Alzheimer's disease therapy. These efforts have successfully led to the identification of a number of promising hits endowed with interesting multifunctional profiles. These include the 4'-metoxytacripyrine (S)-ITH122, able to target cholinesterases (ChEs), beta-amyloid (Aβ) and Ca channels, the racemic 3'-methoxytacripyrimidine EB65F2, the first fully balanced micromolar inhibitor of ChEs and Ca channels, and tacripyrine (-)-SCR1693 a GSK-3β (enzyme involved in tau phosphorylation) inhibitor able to also lower Aβ production in N2a cells."

Journal • Review