LY-411575

SKU: orb1301106

Description

LY-411575

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: Apoptosis,Gamma-secretase
• 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. Bot 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 b the substratees 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 s andard 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℃ith 10 mg mL RNAse. PI (5 mg/mL) is added, an 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 usin the Immunotech Annexin V staining kit followin the manufacturers’ instructions. At least three independent experiments are performed showing similar results < (Only for Reference)

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.
• 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