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.
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LY-411575 Chemische Struktur
CAS. Nr. : 209984-57-6
This product is a controlled substance and not for sale in your territory.
Based on 18 publication(s) in Google Scholar
Other Forms of LY-411575:
LY-411575 isomer 1
In-stock
LY-411575 (isomer 2)
In-stock
LY-411575 (isomer 3)
In-stock
LY-411575 purchased from MedChemExpress. Usage Cited in:
Oncoimmunology. 2018 Aug 23;7(11):e1461303.
[Abstract]
The expression of Oct4 in A549 and H460 cells treated with or without rhIL-17A and these molecular inhibitors (NF-kB inhibitor: PDAC, Notch1 inhibitor: LY411575) are assessed by western blotting.
LY-411575 purchased from MedChemExpress. Usage Cited in:
Oncoimmunology. 2018 Aug 23;7(11):e1461303.
[Abstract]
The expression of Oct4 in A549 and H460 cells treated with or without rhIL-17A and these molecular inhibitors (NF-kB inhibitor: PDAC, Notch1 inhibitor: LY411575) are assessed by western blotting.
Short-term lineage tracing: immunodetection of GFP and the Ins and Gcg hormones in 5-dpf Tg(ascl1b:eGFP-creER T2 ) embryos treated from 3 to 5 dpf with DMSO or with the Notch signaling inhibitor, LY411575.
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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.
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.
LY-411575 Related Antibodies
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.
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
ConcentrationSolventMass
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.
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 μLDMSO 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 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
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.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
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.
[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]
[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]
[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]
[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.
[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
[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.
[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.
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.
Optional Solvent
ConcentrationSolventMass
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
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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