| Identification | Back Directory | [Name]
2-[(1R)-1-[[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl)amino]ethyl]-5-fluoroBenzenebutanoic acid | [CAS]
290315-45-6 | [Synonyms]
BMS 299897
BMS-299897
(BMS 299897
γ-Secretase Inhibitor XXIV, BMS299897
γ-Secretase Inhibitor XXIV, BMS299897 - CAS 290315-45-6 - Calbiochem
2-[(1R)-1-[[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl)amino]ethyl]-5-fluoroBenzenebutanoic acid
Benzenebutanoic acid, 2-[(1R)-1-[[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl)amino]ethyl]-5-fluoro- | [Molecular Formula]
C24H21ClF3NO4S | [MDL Number]
MFCD12963627 | [MOL File]
290315-45-6.mol | [Molecular Weight]
511.94 |
| Chemical Properties | Back Directory | [Boiling point ]
620.0±65.0 °C(Predicted) | [density ]
1.421±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: ≥20mg/mL | [form ]
White solid | [pka]
4.71±0.10(Predicted) | [color ]
white to beige | [InChI]
1S/C24H21ClF3NO4S/c1-15(21-11-7-18(26)13-16(21)3-2-4-24(30)31)29(23-14-19(27)8-12-22(23)28)34(32,33)20-9-5-17(25)6-10-20/h5-15H,2-4H2,1H3,(H,30,31)/t15-/m1/s1 | [InChIKey]
IZAOBRWCUGOKNH-OAHLLOKOSA-N | [SMILES]
Fc1c(cc(cc1)F)N([S](=O)(=O)c3ccc(cc3)Cl)[C@H](C)c2c(cc(cc2)F)CCCC(=O)O |
| Hazard Information | Back Directory | [Uses]
BMS 299897 is a known γ-secretase inhibitor that effectively reduces amyloid β-peptide (Aβ) in transgenic mice and guinea pigs (1,2,3). Studies have shown the possibility of using BMS 299897 in the treatments for Alzheimer’s patients. | [Definition]
ChEBI: 4-[2-[(1R)-1-(N-(4-chlorophenyl)sulfonyl-2,5-difluoroanilino)ethyl]-5-fluorophenyl]butanoic acid is a sulfonamide. | [Biological Activity]
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]. | [in vivo]
BMS-299897 shows dose- and time-dependent reductions of amyloid β-peptide (Aβ) in brain, cerebrospinal fluid (CSF), and plasma in young transgenic mice, with a correlation between brain and CSF Aβ levels. BMS-299897 reduces both brain and plasma Aβ1-40 in APP-YAC mice and increases brain concentrations of APPcarboxy-terminal fragments, consistent with γ-secretase inhibition. BMS-299897, attenuates this Aβ25-35-induced Aβ1-42 seeding and toxicity. BMS-299897 is administered at 0.1-1 nmol/mouse, concomittantly with Aβ25-35 (9 nmol) in male Swiss mice. After one week, the contents in Aβ1-42 and Aβ1-40, and the levels in lipid peroxidation are analyzed in the mouse hippocampus. Mice are submitted to spontaneous alternation, passive avoidance and object recognition to analyze their short- and long-term memory abilities. Aβ25-35 increases Aβ1-42 content (+240%) but fails to affect Aβ1-40. BMS-299897 blocks the increase in Aβ1-42 content and decreased Aβ1-40 levels significantly. The compound does not affect Aβ25-35-induced increase in hippocampal lipid peroxidation. Behaviorally, BMS-299897 blocks the Aβ25-35-induced deficits in spontaneous alternation or novel object recognition, using a 1 h intertrial time interval. The co-administration of the γ-secretase inhibitor BMS-299897, in the 0.1-1 μmol/mouse dose-range, completely blocks the Aβ25-35-induced increase in Aβ1-42 content[1]. | [storage]
Store at -20°C | [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. |
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