1. Neuronal Signaling
    Stem Cell/Wnt
  2. γ-secretase

BMS 299897 

Cat. No.: HY-50883 Purity: 99.35%
Data Sheet SDS Handling Instructions

BMS 299897 is a sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).

For research use only. We do not sell to patients.
BMS 299897 Chemical Structure

BMS 299897 Chemical Structure

CAS No. : 290315-45-6

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $139 In-stock
10 mg $126 In-stock
50 mg $356 In-stock
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

BMS 299897 is a sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).

IC50 & Target

IC50: 7 nM (Aβ, in HEK293 cells)[1]

In Vitro

BMS-299897 reduces the levels of each of the Aβ peptides. At 1 μM, BMS-299897 decreases these peptides to levels ranging from 20 to 50% of the vehicle control. BMS-299897 treatment reduces the portion of QD-BDNF signals moving in the retrograde direction (p=0.0198) with a concomitant increase in the portion of signals moving in the anterograde direction (p=0.0147)[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].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 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
Cell Assay
[2]

BMS-299897 is prepared in DMSO and stored, and then diluted with appropriate medium (final DMSO 0.1%) before use[2].

Neuronal cultures are treated at indicated DIVs for 24 hrs with 1 μM BMS-299897, 2.5 μM sGSM41 or the vehicle DMSO (final concentration: 0.1%) for most of the experiments, or for different periods of time as indicated in specific experiments. Transfections of siRNAs are performed on 100,000 neurons at DIV4 using NTER Nanoparticle transfection system following the protocol provided. The siRNAs used are: 1) siRNA against rat APP, and 2) the MISSION siRNA. Knockdown experiments are optimized by examining both mRNA and protein expression of APP. A knockdown efficiency of 80% at the mRNA level as quantitated with the 7300 Real Time PCR System and 30% at the protein level by immunoblotting is routinely achieved[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

BMS-299897 is solubilized in DMSO, and then brought up to volume in DMSO 40% in distilled water[1].

Mice[1]
Male Swiss OF 1 mice, aged 7-9 weeks and weighing 32±2 g are used. Doses of 0.1, 0.3 and 1 μmol are injected i.c.v. in 1 μL simultaneously with the Aβ25-35 peptide. Animals are used at day 7-9 after i.c.v. injections for behavioral testing or sacrifice, before biochemical measures. All experiments are conducted on separate batch of mice, except spontaneous alternation and passive avoidance, which are done in series in the same animals. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

511.94

Formula

C₂₄H₂₁ClF₃NO₄S

CAS No.

290315-45-6

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 30 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
BMS 299897
Cat. No.:
HY-50883
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