An orally bioavailable sulfonamide compound that acts as a potent, reversible and allosteric y-secretase activity inhibitor with ~15-fold greater selectivity over Notch-1 proteolysis processing (IC50=7.1 and 105.9nM in HEK293-wtAPP) and preferentially inhibits PS1 (presenillin 1)-comprised y-secretase (EC50=8, 108, 286 and 29nM for PS1, Triple PS1-L172M,T281P, L282I, PS2 and Triple PS2-M178L, P287T, I288L), respectively). Shown to reduce the levels of Ab38, Ab40 and Ab42 in Tg2576 mice, Ab40 brain and plasma in APP-YAC mice (ED50=30 and 16mg/kg, p.o.) and Abtotal brain, CSF and plasma in guinea pigs (ED50=30mg/kg, i.p.).
Formula:C₂₄H₂₁ClF₃NO₄S
Molecular Weight:511.9
Solubility:DMSO (50mg/ml)
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
