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BMS 299897

In stock
Catalog No.
A4400
γ--secretase inhibitor, potent and orally active
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$216.00
In stock
10mg
$196.00
In stock
50mg
$555.00
In stock

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BMS-299897 is a selective inhibitor of γ-secretase with IC50 value of 12 nM [1].

γ-secretase is an intergral membrane protein whose well-known substrate is amyloid precursor protein and involves in the process of cleaving single-pass transmembrane proteins at residues with the transmembrane domain. It has been revealed thatγ-secretase cleave APP in any of multiple sites and generate a 39 to 42 amino acids long peptide, among which Aβ40 is the most common isoform and Aβ42 is the most susceptible to conformational changes leading to amyloid fibrillogenesis. Many studies have shown that reduction of brain Aβ synthesis by gamma-secretase inhibitors is a promising approach for the Alzheimer's disease treatment [1] [2].

BMS 299897 is a selective inhibitorγ-secretase. When tested HEKwt culture with BMS-299897, the expression of Aβ(1-40) in culture supernatant had a robust rise throughγ-secretase inhibition [3].

In male Swiss mice model with intracerebroventricular (i.c.v.) injection of Aβ(25-35) which induced Alzheimer's disease pathomimetic toxicity, administration of BMS-299897 markedly attenuated Aβ(1-42)-whose accumulation marginally contributed to the toxicity or long-term memory deficits-seeding and toxicity induced by Aβ(25-35) through inhibiting γ-secretase [4]. When tested with Tg2576 mice, oral administration of BMS-299897 markedly reduced Abeta peptide concentrations by inhibitingγ-secretase [5] [2].

References:
[1].  Anderson, J.J., et al., Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Biochem Pharmacol, 2005. 69(4): p. 689-98.
[2].  Barten, D.M., et al., Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor. J Pharmacol Exp Ther, 2005. 312(2): p. 635-43.
[3].  Burton, C.R., et al., The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression. J Biol Chem, 2008. 283(34): p. 22992-3003.
[4].  Meunier, J., et al., The gamma-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Abeta1-42 seeding and short-term memory deficits in the Abeta25-35 mouse model of Alzheimer's disease. Eur J Pharmacol, 2013. 698(1-3): p. 193-9.
[5].  Goldstein, M.E., et al., Ex vivo occupancy of gamma-secretase inhibitors correlates with brain beta-amyloid peptide reduction in Tg2576 mice. J Pharmacol Exp Ther, 2007. 323(1): p. 102-8.

Chemical Properties

Physical AppearanceWhite solid
StorageStore at -20°C
M.Wt511.94
Cas No.290315-45-6
FormulaC24H21ClF3NO4S
SolubilitySoluble in DMSO
Chemical Name4-[2-[(1R)-1-(N-(4-chlorophenyl)sulfonyl-2,5-difluoroanilino)ethyl]-5-fluorophenyl]butanoic acid
SDFDownload SDF
Canonical SMILESCC(C1=C(C=C(C=C1)F)CCCC(=O)O)N(C2=C(C=CC(=C2)F)F)S(=O)(=O)C3=CC=C(C=C3)Cl
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

HEKwt culture

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

0.01 ~ 10000 nM

Applications

When tested HEKwt culture with BMS-299897, the expression of Aβ-(1-40) in culture supernatant had a robust rise due to γ-secretase inhibition.

Animal experiment [2]:

Animal models

APP-YAC mice

Dosage form

1.5 ~ 150 mg/kg; p.o.

Applications

In APP-YAC mice, BMS 299897 dose-dependently reduced brain and plasma Aβ.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Burton CR, Meredith JE, Barten DM, Goldstein ME, Krause CM, Kieras CJ, Sisk L, Iben LG, Polson C, Thompson MW, Lin XA, Corsa J, Fiedler T, Pierdomenico M, Cao Y, Roach AH, Cantone JL, Ford MJ, Drexler DM, Olson RE, Yang MG, Bergstrom CP, McElhone KE, Bronson JJ, Macor JE, Blat Y, Grafstrom RH, Stern AM, Seiffert DA, Zaczek R, Albright CF, Toyn JH. The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression. J Biol Chem. 2008 Aug 22;283(34):22992-3003.

[2]. Anderson JJ, Holtz G, Baskin PP, Turner M, Rowe B, Wang B, Kounnas MZ, Lamb BT, Barten D, Felsenstein K, McDonald I, Srinivasan K, Munoz B, Wagner SL. Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Biochem Pharmacol. 2005 Feb 15;69(4):689-98.

Biological Activity

Description BMS 299897 is a potent and orally active inhibitor of γ-secretase with IC50 value of 12 nM.
Targets γ-secretase          
IC50 12 nM          

Quality Control

Quality Control & MSDS

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Chemical structure

BMS 299897