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Reactivos e instrumentos para inmunología, biología celular y biología molecular.

LY-411575 [209984-57-6]

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Referencia HY-50752-5mg

embalaje : 5mg

Contact local distributor :

Teléfono : +1 850 650 7790

Marca : MedChemExpress

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Contact local distributor :

Teléfono : +1 850 650 7790

Descripciòn

LY-411575 is a potent γ-secretase inhibitor with IC₅₀ of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with an IC₅₀ of 0.39 nM.

IC₅₀ & Target

IC50: 0.078 nM (γ-secretase in membrane), 0.082 nM (γ-secretase cell-based), 0.39 nM (Notch S3 cleavage cell-based)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	EC₅₀	114 pM Compound: LY-411575	Reduction of human wild type PS1-induced amyloid beta-40 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control Reduction of human wild type PS1-induced amyloid beta-40 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control	[PMID: 17573346]
CHO	EC₅₀	135 pM Compound: LY-411575	Reduction of human wild type PS1-induced amyloid beta-42 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control Reduction of human wild type PS1-induced amyloid beta-42 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control	[PMID: 17573346]
CHO	EC₅₀	352 pM Compound: LY-411575	Reduction of human PS1 delta exon9 mutant-induced amyloid beta-42 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control Reduction of human PS1 delta exon9 mutant-induced amyloid beta-42 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control	[PMID: 17573346]
CHO	EC₅₀	358 pM Compound: LY-411575	Reduction of human PS1 delta exon9 mutant-induced amyloid beta-40 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control Reduction of human PS1 delta exon9 mutant-induced amyloid beta-40 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control	[PMID: 17573346]
HEK293	EC₅₀	119 pM Compound: LY-411575	Inhibition of gamma secretase in human HEK293 cells assessed as amyloid beta 40 production Inhibition of gamma secretase in human HEK293 cells assessed as amyloid beta 40 production	[PMID: 17573346]
HEK293	IC₅₀	<0.0003 μM Compound: 42; LY-411,575	Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay	[PMID: 29359565]
HEK293	IC₅₀	<0.3 nM Compound: 42; LY-411,575	Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay	[PMID: 29359565]
HEK293	IC₅₀	0.01 μM Compound: 42; LY-411,575	Inhibition of human SPPL2a expressed in HEK293 cells using GAL4-VP16 fusedTNFalpha (1 to 76)-NTF as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay Inhibition of human SPPL2a expressed in HEK293 cells using GAL4-VP16 fusedTNFalpha (1 to 76)-NTF as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay	[PMID: 29359565]
HEK293	IC₅₀	0.08 nM Compound: 19; LY-411575	Inhibition of gamma secretase in HEK293 cells expressing APP 695 assessed as reduction in amyloid beta levels after 5 hrs by Western blot analysis Inhibition of gamma secretase in HEK293 cells expressing APP 695 assessed as reduction in amyloid beta levels after 5 hrs by Western blot analysis	[PMID: 27045975]
HEK293	IC₅₀	0.39 nM Compound: 19; LY-411575	Inhibition of gamma secretase mediated Notch signaling in HEK293 cells after 5 hrs by Western blot analysis Inhibition of gamma secretase mediated Notch signaling in HEK293 cells after 5 hrs by Western blot analysis	[PMID: 27045975]
HEK293	IC₅₀	1.2 μM Compound: LY411575	Modulation of gamma-secretase in HEK293 cells expressing guinea pig Swedish mutant SFV-APP695sw coexpressing DLL4 assessed as inhibition of notch processing in human TE671 cells after 3 days by dual-cell luciferase reporter gene assay Modulation of gamma-secretase in HEK293 cells expressing guinea pig Swedish mutant SFV-APP695sw coexpressing DLL4 assessed as inhibition of notch processing in human TE671 cells after 3 days by dual-cell luciferase reporter gene assay	[PMID: 24139583]
Huh-7	IC₅₀	80 μM Compound: 118, LY-411575	Antimalarial activity against Plasmodium berghei ANKA infected in human Huh7 cells after 24 hrs by qRT-PCR Antimalarial activity against Plasmodium berghei ANKA infected in human Huh7 cells after 24 hrs by qRT-PCR	[PMID: 22122518]
SH-SY5Y	IC₅₀	1 nM Compound: 15 LY-411575	Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay	[PMID: 19694467]
SH-SY5Y	IC₅₀	1 nM Compound: 15 LY-411575	Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells	[PMID: 19694467]

In Vitro

LY-411575 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^[2].
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^[4]. LY411575 significantly attenuates EMT by inhibiting the Notch signaling activation in vitro^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Solvente y solubilidad

In Vitro:

DMSO : ≥ 100 mg/mL (208.56 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.0856 mL	10.4280 mL	20.8559 mL
5 mM	0.4171 mL	2.0856 mL	4.1712 mL
10 mM	0.2086 mL	1.0428 mL	2.0856 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Pureza y Documentación

Purity: 98.68%

Ficha de datos (283 KB) SDS (393 KB)

COA (254 KB) HNMR (141 KB) LCMS (97 KB) Elemental Analysis Report (112 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Wong GT, et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem. 2004 Mar 26;279(13):12876-82. [Content Brief]

[2]. Otoguro T, et al. Inhibitory effect of presenilin inhibitor LY411575 on maturation of hepatitis C virus core protein, production of the viral particle and expression of host proteins involved in pathogenicity. Microbiol Immunol. 2016 Nov;60(11):740-753 [Content Brief]

[3]. Curry CL, et al. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene. 2005 Sep 22;24(42):6333-44. [Content Brief]

[4]. Zhang J, et al. Notch signaling modulates proliferative vitreoretinopathy via regulating retinal pigment epithelial-to-mesenchymal transition. Histochem Cell Biol. 2017 Mar;147(3):367-375. [Content Brief]

[5]. Hyde LA, et al. Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse. J Pharmacol Exp Ther. 2006 Dec;319(3):1133-43. [Content Brief]

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LY-411575 [209984-57-6]

Referencia HY-50752-5mg

Contact local distributor :

Marca : MedChemExpress

Contact local distributor :

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