LY-411575

SKU: orb1301106

Description

LY-411575 is a potent and selective γ-secretase inhibitor, demonstrating low nanomolar IC50 values in both membrane and cell-based assays for suppressing Notch cleavage. It is widely used in vitro and in vivo to investigate the Notch signaling pathway in cancer, neurology, and developmental biology research.

Research Area

Cell Biology, Neuroscience, Protein Biochemistry, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 209984-57-6
• MW: 479.48
• Purity: 99.23%
• Formula: C₂₆H₂₃F₂N₃O₄
• SMILES: C[C@H](NC(=O)[C@@H](O)c1cc(F)cc(F)c1)C(=O)N[C@H]1c2ccccc2-c2ccccc2N(C)C1=O
• Target: Gamma-secretase,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.88 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:35.71 mg/mL (74.48 mM);Ethanol:11 mg/mL (22.94 mM)

Bioactivity

• Target IC50:
  γ-secretase (cell-based assay):0.082 nM|γ-secretase (membrane-based):0.078 nM|Notch S3 cleavage:0.39 nM
• In Vivo:
  10 mg/kg oral dose of LY-411575 decreases brain and plasma Aβ40 and -42 dose-dependently. LY-411575 reduces cortical Aβ40 in young (preplaque) transgenic CRND8 mice (ED50 ≈ 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The therapeutic window is similar after oral and subcutaneous administration and in young and aged CRND8 mice. Both the thymus and intestinal side effects are reversible after a 2-week washout period. Three-week treatment with 1 mg/kg LY411575 reduces cortical Aβ40 by 69% without inducing intestinal effects, although a previously unreported change in coat color is observed.
• In Vitro:
  LY-411575 inhibits γ-secretase which can be assessed by the substrates like amyloid precursor protein (APP) and Notch S3 cleavage. LY-411575, which blocks Notch activation, results in apoptosis in primary and immortalized KS cells.
• Cell Research:
  DNA/PI staining is performed using standard methodologies. Briefly, 1 × 106 cells are permeabilized with 100% ethanol in the presence of 15% FBS. The cells are washed and then treated for 15 minutes at 37 °C with 10 mg/mL RNAse. PI (5 mg/mL) is added, and the cells incubated for 1 hour at 4 °C prior to analysis by flow cytometry with 10 000 cells analysed per gated determination. The results are confirmed using the Immunotech Annexin V staining kit following the manufacturers’ instructions. At least three independent experiments are performed showing similar results.

Storage & Handling

• Storage: keep away from moisture,keep away from direct sunlight | 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

Apoptosis, Inhibitor, Gammasecretase, Gamma secretase, inhibit, Notch S3 cleavage, Notch, LY411575, LY-411575, LY 411575, γ secretase (cell-based), γ secretase (membrane-based), γ-secretase

Compound Identifiers

PubChem CID

10435235