LY-411575

SKU: orb1225693

Description

A potent γ-secretase inhibitor that has an IC50 value of 119 pM for reduction of Aβ levels in APP-transfected cell lines; dose dependently reduces Aβ(1-40) and Aβ(1-42) in the brain, CSF, and plasma of Tg2576 mice; reduces cortical Abeta(40) in young transgenic CRND8 mice with ED50 of 0.6 mg/kg, and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg).Alzheimer's Disease Preclinical.

Key Properties

• CAS Number: 209984-57-6
• MW: 479.4753
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₃F₂N₃O₄
• SMILES: C[C@@H](C(N[C@H]1C2=CC=CC=C2C3=CC=CC=C3N(C)C1=O)=O)NC([C@H](C4=CC(F)=CC(F)=C4)O)=O
• Target: γ-secretase
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  LY-411, 575 (10 mg/kg) decreases brain and plasma Aβ40 and-42 robustly when chronically administered to TgCRND8 mice. LY411, 575 reduces cortical Aβ40 in young transgenic CRND8 mice (ED50 appr 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The extent of intestinal goblet cell hyperplasia induced by LY411, 575 (10 mg/kg) is similar in young and aged mice. LY411575 inhibits mouse proliferative vitreoretinopathy (PVR) formation In vivo.
• In Vitro:
  LY-411, 575 blocks Notch activation, and results in apoptosis in primary and immortalized KS cells. LY-411, 575 (500 μM) induces G2/M growth arrest SLK cells. LY411575 treatment significantly decreases the amounts of intracellular HCV RNA with IC50 of 0.56 ± 0.20 μM and extracellular HCV particles. LY411575 (0-40 nM) alone or in combination with BMS-790052 (0-40 pM) decreases supernatant infectious titers in a dose-dependent manner, and is synergistic regarding production of infectious virus. LY411575 (10 μM) treatment impairs ROS production in HCVcc-infected cells. LY411575 significantly attenuates EMT by inhibiting the Notch signaling activation in vitro.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY411575 | LY 411575

Quick Database Links

Gene Symbol

γ-secretase