Avagacestat

SKU: orb1300938

Description

Avagacestat (BMS-708163) is an orally active, potent, and selective γ-secretase inhibitor, showing preferential inhibition of Aβ40/Aβ42 production over Notch signaling. It has been utilized in preclinical and clinical phase 2 research for investigating Alzheimer's disease pathogenesis and potential therapeutic strategies.

Research Area

Neuroscience, Protein Biochemistry, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1146699-66-2
• MW: 520.89
• Purity: 99.77% (May vary between batches)
• Formula: C₂₀H₁₇ClF₄N₄O₄S
• SMILES: NC(=O)[C@@H](CCC(F)(F)F)N(Cc1ccc(cc1F)-c1ncon1)S(=O)(=O)c1ccc(Cl)cc1
• Target: Gamma-secretase
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+90% Corn Oil:4 mg/mL (7.68 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:96 mg/mL (184.3 mM)

Bioactivity

• Target IC50:
  γ-secretase (Aβ42):0.27 nM|γ-secretase (Aβ40):0.3 nM
• In Vivo:
  Oral administration of BMS-708163 significantly reduces Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs. BMS-708163 has no dose-limiting effects in dogs (3 mg/kg during 6 months), with a high brain to plasma ratio (2.4).
• In Vitro:
  BMS-708163 exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value.
• Cell Research:
  BMS-708163 is dissolved in DMSO. The cell viability is assessed using a tetrazolium salt (WST-8)-based colorimetric assay from the Cell Counting Kit 8 (CCK-8). The cells are seeded into 96-well plates at an initial density of 5×103 cells/well and cultured for 24 h, after which the cells are cultured with DMSO, increased concentrations of gefitinib or BMS708163, BIBW2992, or the combination of BMS708163 and BIBW2992 for an additional 48 h. The A450 is measured in a microplate reader after 10 μL of CCK-8 solution is added and incubated for 1 h. The percentage of growth is shown relative to untreated controls.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Avagacestat, BMS 708163, BMS708163, BMS-708163, Gamma secretase, Gammasecretase, inhibit, Notch, Inhibitor, γ secretase(Aβ40), γ secretase(Aβ42), γ-secretase

Compound Identifiers

PubChem CID

46883536