HY-50752-5mg | LY-411575 [209984-57-6] Biotrend

Beschreibung

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 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	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	0.01 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]

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^[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.

In Vivo

LY-411,575 (10 mg/kg) decreases brain and plasma Aβ40 and -42 robustly when chronically administered to TgCRND8 mice^[1]. 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^[3]. LY411575 inhibits mouse proliferative vitreoretinopathy (PVR) formation in vivo^[5].

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

Molekulargewicht

479.48

Formel

C₂₆H₂₃F₂N₃O₄

CAS. Nr.

209984-57-6

Appearance

Solid

Color

White to off-white

SMILES

O=C1[C@@H](NC([C@@H](NC([C@H](C2=CC(F)=CC(F)=C2)O)=O)C)=O)C3=CC=CC=C3C(C=CC=C4)=C4N1C

Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 33.33 mg/mL (69.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

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.

Molaritätsrechner
Verdünnungsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Reinheit & Dokumentation

Purity: 98.68%

Select Batch:

SDS (393 KB)

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

Handling Instructions (2659 KB)

Verweise

[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]

Tierverwaltung ^[3]	Mice from the aged cohort (16-26 months old) are either retired breeders or experimentally naive mice. Before dosing begin and for the duration of the study, mice are singly housed with a plastic igloo and nesting material. Mice are sacrificed 2 to 4 h after their final dosing. For oral dosing, LY411,575 and LY-D are formulated as 10 mg/mL solutions and diluted 1:10 with 0.4% methycellulose. In the case of subcutaneous dosing, the 10 mg/mL stock solution is diluted 1:10 with 20% hydroxyl-propyl-β-cyclodextrin. If necessary, serial dilutions are made from the 1 mg/mL solution using the appropriate 1:10 vehicle. The dosing volume is 10 mL/kg. After oral administration of 10 mg/kg LY411,575, inhibition of plasma Aβ is still significant 24, but not 48, h after dosing, so in an effort to maintain continuous γ-secretase inhibition, LY411,575 and LY-D are dosed once per day in all studies. MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Verweise	[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]

Tierverwaltung
^[3]

Mice from the aged cohort (16-26 months old) are either retired breeders or experimentally naive mice. Before dosing begin and for the duration of the study, mice are singly housed with a plastic igloo and nesting material. Mice are sacrificed 2 to 4 h after their final dosing. For oral dosing, LY411,575 and LY-D are formulated as 10 mg/mL solutions and diluted 1:10 with 0.4% methycellulose. In the case of subcutaneous dosing, the 10 mg/mL stock solution is diluted 1:10 with 20% hydroxyl-propyl-β-cyclodextrin. If necessary, serial dilutions are made from the 1 mg/mL solution using the appropriate 1:10 vehicle. The dosing volume is 10 mL/kg. After oral administration of 10 mg/kg LY411,575, inhibition of plasma Aβ is still significant 24, but not 48, h after dosing, so in an effort to maintain continuous γ-secretase inhibition, LY411,575 and LY-D are dosed once per day in all studies.

MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.

Verweise

[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]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.0856 mL	10.4280 mL	20.8559 mL	52.1398 mL
	5 mM	0.4171 mL	2.0856 mL	4.1712 mL	10.4280 mL
	10 mM	0.2086 mL	1.0428 mL	2.0856 mL	5.2140 mL
	15 mM	0.1390 mL	0.6952 mL	1.3904 mL	3.4760 mL
	20 mM	0.1043 mL	0.5214 mL	1.0428 mL	2.6070 mL
	25 mM	0.0834 mL	0.4171 mL	0.8342 mL	2.0856 mL
	30 mM	0.0695 mL	0.3476 mL	0.6952 mL	1.7380 mL
	40 mM	0.0521 mL	0.2607 mL	0.5214 mL	1.3035 mL
	50 mM	0.0417 mL	0.2086 mL	0.4171 mL	1.0428 mL
	60 mM	0.0348 mL	0.1738 mL	0.3476 mL	0.8690 mL

LY-411575 Related Classifications

Neuronal Signaling Stem Cell/Wnt Apoptosis
Organoid γ-secretase Notch Apoptosis

LY-411575 [209984-57-6]

Katalog-Nummer HY-50752-5mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Other Forms of LY-411575:

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

LY-411575 Related Classifications

Keywords:

Sie könnten auch an folgenden Produkten interessiert sein:

LY-411575 [209984-57-6]

Katalog-Nummer HY-50752-5mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Other Forms of LY-411575:

LY-411575 Related Antibodies

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

LY-411575 Related Classifications

Keywords:

Sie könnten auch an folgenden Produkten interessiert sein: