Semagacestat

SKU: orb1301052

Description

Semagacestat

Research Area

Neuroscience, Protein Biochemistry, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 425386-60-3
• MW: 361.44
• Purity: 99.90%
• Formula: C₁₉H₂₇N₃O₄
• SMILES: CC(C)[C@H](O)C(=O)N[C@@H](C)C(=O)N[C@H]1c2ccccc2CCN(C)C1=O
• Target: Beta Amyloid,Gamma-secretase
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2.5 mg/mL (6.92 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:67 mg/mL (185.37 mM);Ethanol:39 mg/mL (107.9 mM)

Bioactivity

• Target IC50:
  γ-secretase Aβ38):12.0 nM|γ-secretase Aβ42):10.9 nM|γ-secretase Aβ40):12.1 nM
• In Vivo:
  Oral administration of Semagacestat (1 mg/kg) to 5.5-month old APP-transgenic Tg2576 mice significantly ameliorates memory deficits on spatial working memory usin the Y-maze task, which disappears after 8 days subchronic dosing. LY450139 decreases hippocampal levels of both Aβ42 and Aβ40 at 10 mg/kg (22-23% reduction) and 30 mg/kg (36-41% reduction) and increases β-CTF at 0.3-10 mg/kg in a dose dependent manner with no Inhibition o the processing of Other γ-secretase substratees, such as Notch, N-cadherin or EphA4, in the brain, but impairs normal cognition in wild-type mice and 3-month-old Tg2576 mice failing to restore cognitive deficits in the Y-maze test.
• In Vitro:
  Semagacestat reduce the secretion of Aβ42, Aβ40 and Aβ38 from H4 human glioma cells stably overexpressing human wild-type APP int the culture medium, with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, respectively without affecting cell viability. Semagacestat also increases β-CTF in cell lysates with ECmax of 16.0 nM, an the increase can be unexpectedly attenuated at high concentration . Semagacestat inhibits Notch signaling with IC50 of 14.1 nM, and shows minimal Notch-sparing selectivity with Notch IC50 Aβ42 IC50 only 1.3. Semagacestat causes a concentration dependent decrease in Aβ40 secreted int the medium with IC50 of 111 nM from murine CTX expressing endogenous murine APP, but murine Aβ42 formation in CTX is roughly 12-fold less than Aβ40 in accordance with data for neurons from wild type mice.
• Cell Research:
  Cells are incubated with Semagacestat for 24 hours. For detection of cell viability the percentage of viable cells is quantified by their capacity to reduce 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) following incubation with 0.5 mg mL MTT for 60 minutes. Fo the detection of sAPP species, cells are lysed and analysed by western blotting.(Only for Reference)

Storage & Handling

• Storage: 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

BetaAmyloid, Beta Amyloid, Amyloid-β, bAmyloid, b Amyloid, Abeta, LY 450139, LY450139, LY-450139, inhibit, Inhibitor, Notch, Gammasecretase, Gamma secretase, Semagacestat, β Amyloid, βAmyloid, β-amyloid peptide, γ secretase(Aβ42), γ secretase(Aβ38), γ secretase(Aβ40), γ-secretase

Compound Identifiers

PubChem CID

9843750