General description

A cell-permeable sulfonamide compound that preferentially inhibits γ-secretase activity toward APP CTF over Notch-1 (IC₅₀ against APP_SW CTF and murine δE-Notch processing = 7.1 and 105.9 nM, respectively, in HEK293) in a presenillin 1-/PS1-selective manner (IC₅₀ = 8 and 308 nM against APP_SW processing in PS1^-/-PS2^-/-MEF expressing human PS1 and PS2, respectively). BMS-299897 is shown to be orally available, readily cross blood-brain-barrier (﹤15 min), and effectively suppress plasma and brain Aβ level in transgenic mice bearing normal human APP (APP-YAC) or APP_SW/APP_K670N/M671L (Tg2576) in a time- and dose-dependent manner (optimal p.o. dose 100 mg/kg) in vivo. However, BMS-299897 is not effective in reducing Aβ in aged, plaque-bearing murine brain and long-term daily drug dosing is reported to result in increased drug metabolizing activity in mice.

A cell-permeable sulfonamide compound that preferentially inhibits cellular γ-secretase cleavage of APP CTF over Notch-1 (IC₅₀ = 7.1 and 105.9 nM, respectively) in a presenillin 1-/PS1-selective manner (IC₅₀ = 8 and 308 nM against PS1 and PS2, respectively). BMS-299897 is shown to be orally available, readily cross blood-brain-barrier (﹤15 min), and effectively suppress plasma and brain Aβ level in human APP-bearing transgenic mice in a time- and dose-dependent manner (optimal p.o. dose 100 mg/kg) in vivo.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Zhao, B., et al. 2008. J. Biol. Chem. 283, 2927.Barten, D.M., et al. 2005. J. Pharmacol. Exp. Ther.312, 635.Anderson, J.J., et al. 2005. Biochem. Pharmacol.69, 689.

Packaging

5 mg in Glass bottle

Packaged under inert gas

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Standard Handling (A)