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LY-411575

Catalog No. T6063   CAS 209984-57-6
Synonyms: LY411575

LY-411575, a potent γ-secretase inhibitor, is with IC50 of 0.078 nM in the membrane and 0.082 nM in cell-based. It also suppresses Notch clevage with IC50 of 0.39 nM.

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LY-411575 Chemical Structure
LY-411575, CAS 209984-57-6
Pack Size Availability Price/USD Quantity
2 mg In stock $ 38.00
5 mg In stock $ 61.00
10 mg In stock $ 107.00
25 mg In stock $ 222.00
50 mg In stock $ 432.00
100 mg In stock $ 639.00
1 mL * 10 mM (in DMSO) In stock $ 63.00
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Purity: 99.38%
Purity: 98.35%
Purity: 97.03%
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Biological Description
Chemical Properties
Storage & Solubility Information
Description LY-411575, a potent γ-secretase inhibitor, is with IC50 of 0.078 nM in the membrane and 0.082 nM in cell-based. It also suppresses Notch clevage with IC50 of 0.39 nM.
Targets&IC50 Notch S3 cleavage:0.39 nM, γ-secretase (cell-based assay):0.082 nM, γ-secretase (membrane-based):0.078 nM
In vitro LY-411575 inhibits γ-secretase which can be assessed by the substrates like amyloid precursor protein (APP) and Notch S3 cleavage. [1] LY-411575, which blocks Notch activation, results in apoptosis in primary and immortalized KS cells. [2]
In vivo 10 mg/kg oral dose of LY-411575 decreases brain and plasma Aβ40 and -42 dose-dependently. [1] 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. [3]
Kinase Assay Assays for Aβ and NICD: Procedures for measuring γ-secretase activity in membranes prepared from HEK293 cells expressing APP have been described previously (Zhang L et al Biochemistry 40, 5049-5055). Intact HEK293 cells expressing either APP or NΔE are treated with various concentrations of LY- 411,575 for 4 hours at 37 °C. In the case of cells expressing NΔE, cells are lysed, the cell lysates are separated on a 4-12% NuPAGE gel, and the processed NICD fragment is detected via Western blot with a cleavage site-specific antibody. The inhibition of NICD production is quantified by spot densitometric analysis using FluorChem. In the case of cells expressing APP, the conditioned medium is collected, centrifuged at 10,000 × g for 5 minutes to remove cell debris, and stored at -20 °C prior to the determination of Aβ levels. Aβ40 and -42 produced in HEK293 membrane- and cell-based assays, as well as plasma Aβ40 and cortex Aβ40 from TgCRND8 mice, are analyzed without pretreatment using an electrochemiluminescence detection-based immunoassay. Plasma Aβ42 is measured by enzyme-linked immunosorbent assay. A commercially available enzyme-linked immunosorbent assay kit is used to measure cortex Aβ42 according to the manufacturer''s instructions.
Cell Research DNA/PI staining is performed using standard methodologies. Briefly, 1 &times; 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&rsquo; instructions. At least three independent experiments are performed showing similar results.</(Only for Reference)
Synonyms LY411575
Molecular Weight 479.48
Formula C26H23F2N3O4
CAS No. 209984-57-6

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 88 mg/mL (183.5 mM)

Ethanol: 11 mg/mL (22.9 mM)

TargetMolReferences and Literature

1. Wong GT, et al, J Biol Chem, 2004, 279(13), 12876-12882. 2. Curry CL, et al, Oncogene, 2005, 24(42), 6333-6344. 3. Hyde LA, et al, J Pharmacol Exp Ther, 2006, 319(3), 1133-1143. 4. Yang D L, Zhang Y, He L, et al. Demethylzeylasteral (T-96) Initiates Extrinsic Apoptosis Against Prostate Cancer cells by Inducing ROS-Mediated ER Stress and Suppressing Autophagic Flux[J]. 2021

TargetMolCitations

1. Yang D L, Zhang Y, He L, et al. Demethylzeylasteral (T-96) Initiates Extrinsic Apoptosis Against Prostate Cancer cells by Inducing ROS-Mediated ER Stress and Suppressing Autophagic Flux. Biological Research. 2021, 54(1): 1-14. 2. Zhang S, Lou H, Lu H, et al.Characterization of Proliferation Medium and Its Effect on Differentiation of Muscle Satellite Cells from Larimichthys crocea in Cultured Fish Meat Production.Fishes.2023, 8(9): 429.

Related compound libraries

This product is contained In the following compound libraries:
Inhibitor Library Anti-Neurodegenerative Disease Compound Library Anti-Colorectal Cancer Compound Library Cancer Cell Differentiation Compound Library Anti-Cancer Compound Library Anti-Aging Compound Library Bioactive Compound Library Anti-Alzheimer's Disease Compound Library Stem Cell Differentiation Compound Library Anti-Prostate Cancer Compound Library

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Keywords

LY-411575 209984-57-6 Apoptosis Neuroscience Proteases/Proteasome Stem Cells Gamma-secretase Inhibitor Gamma secretase γ-secretase Notch LY411575 LY 411575 inhibit inhibitor

 

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