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Purity: ≥98%
BMS 299897 is a novel and potent sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP). BMS-299897 blocked the increase in Aβ(1-42) content and decreased Aβ(1-40) levels significantly. The compound did not affect Aβ(25-35)-induced increase in hippocampal lipid peroxidation. Behaviorally, BMS-299897 blocked the Aβ(25-35)-induced deficits in spontaneous alternation or novel object recognition, using a 1h intertrial time interval. BMS-299896 failed to affect the passive avoidance impairments or novel object recognition, using a 24h intertrial time interval. These results confirmed that Aβ(25-35) injection provoked an accumulation in endogenous Aβ(1-42), an effect blocked by γ-secretase inhibition. This Aβ(1-42) accumulation marginally contributed to the toxicity or long-term memory deficits. However, since the seeded Aβ(1-42) affected short-term memory, the rapid Aβ(25-35) injection Alzheimer's disease model could be used to screen the activity of new secretase inhibitors.
| ln Vitro |
Every Aβ peptide has its levels lowered by BMS-299897. BMS-299897 decreased these peptides to 20% to 50% of vehicle control levels at a dose of 1 μM. The QD-BDNF signal's retrograde-moving portion (p=0.0198) was decreased by the BMS-299897 treatment, although its anterograde-moving portion (p=0.0147) increased [2].
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| ln Vivo |
In the brain, cerebrospinal fluid (CSF), and plasma of young transgenic mice, BMS-299897 demonstrates a dose- and time-dependent decrease in amyloid beta-peptide (Aβ), with a link between brain and CSF Aβ levels. In APP-YAC mice, BMS-299897 decreased Aβ1-40 in the brain and plasma and raised APP carboxyl-terminal fragment concentrations in the brain, which is consistent with γ-secretase inhibition. BMS-299897 reduces the toxicity and Aβ1-42 seeding caused by Aβ25-35. Aβ25-35 (9 nmol) and BMS-299897 were given to male Swiss mice at a dose of 0.1–1 nmol/mouse concurrently. A week later, the mice's hippocampal lipid peroxidation level and the contents of Aβ1-42 and Aβ1-40 were examined. To assess the short- and long-term memory capacities of mice, experiments including spontaneous alternation, passive avoidance, and object recognition were conducted. Aβ25-35 has no effect on Aβ1-40 but raises the content of Aβ1-42 by +240%. BMS-299897 considerably lowers Aβ1-40 levels and prevents the rise in Aβ1-42 content. The chemical in question has no effect on the rise in hippocampus lipid peroxidation generated by Aβ25-35. Using a 1-hour inter-trial delay, BMS-299897 behaviorally inhibits Aβ25-35-induced spontaneous alternation or impairments in novel object identification. The γ-secretase inhibitor BMS-299897, when administered in conjunction with Aβ25-35, totally prevents the increase in Aβ1-42 content in mice at doses between 0.1 and 1 μmol/mouse [1].
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| References |
[1]. Meunier J, et al. The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's d
[2]. Weissmiller AM, et al. A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP. PLoS One. 2015 Feb 24;10(2):e0118379 |
| Molecular Formula |
C24H21NO4F3SCL
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|---|---|
| Molecular Weight |
511.94104
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| CAS # |
290315-45-6
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| SMILES |
O=C(O)CCCC1=CC(F)=CC=C1[C@H](N(C2=CC(F)=CC=C2F)S(=O)(C3=CC=C(Cl)C=C3)=O)C
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| InChi Key |
IZAOBRWCUGOKNH-OAHLLOKOSA-N
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| InChi Code |
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
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| Chemical Name |
(R)-4-(2-(1-(4-chloro-N-(2,5-difluorophenyl)phenylsulfonamido)ethyl)-5-fluorophenyl)butanoic acid
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| Synonyms |
BMS299897; BMS 299897; BMS-299897
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 30 mg/mL (~58.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9534 mL | 9.7668 mL | 19.5335 mL | |
| 5 mM | 0.3907 mL | 1.9534 mL | 3.9067 mL | |
| 10 mM | 0.1953 mL | 0.9767 mL | 1.9534 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Differential effects of BMS-299897 and sGSM41 on APP processing.PLoS One.2015 Feb 24;10(2):e0118379. |
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 BMS-299897, not sGSM41, induces deficits in retrograde axonal trafficking of QD-BDNF.PLoS One.2015 Feb 24;10(2):e0118379. |
 Knockdown of APP rescues deficits in velocity and directionality of axonally transported QD-BDNF induced by BMS-299897.PLoS One.2015 Feb 24;10(2):e |
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