| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
LY-411575 isomer 1 targets gamma-secretase, a multi-subunit protease complex that cleaves the amyloid precursor protein (APP) to generate amyloid-beta (Abeta) peptides. The accumulation of Abeta peptides, particularly Abeta42, is a hallmark of Alzheimer's disease. By inhibiting gamma-secretase, LY-411575 isomer 1 reduces the production of Abeta peptides, making it a valuable tool for studying Alzheimer's disease pathogenesis. The compound is a potent inhibitor with an IC₅0 of 0.078 nM (membrane-based) and 0.082 nM (cell-based).
|
|---|---|
| ln Vitro |
In vitro, LY-411575 isomer 1 is a potent gamma-secretase inhibitor with IC₅0 values of 0.078 nM (membrane-based) and 0.082 nM (cell-based). By inhibiting gamma-secretase, the compound reduces the production of amyloid-beta peptides. Its high potency makes it a valuable tool for studying the role of gamma-secretase in Alzheimer's disease and other conditions. The compound is an enantiomer of LY411575.
|
| ln Vivo |
In vivo studies of LY-411575 isomer 1 are likely focused on evaluating its effects in animal models of Alzheimer's disease. By reducing the production of amyloid-beta peptides, the compound may have potential for treating Alzheimer's disease. However, gamma-secretase inhibitors can have significant off-target effects due to the role of gamma-secretase in other signaling pathways, such as Notch signaling. Further in vivo studies are needed to fully characterize its efficacy, safety, and pharmacokinetic profile.
|
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, LY-411575 isomer 1 can be evaluated using gamma-secretase activity assays that measure the cleavage of APP or a synthetic substrate. The compound is incubated with gamma-secretase enzyme preparations (membrane fractions or purified enzyme) and substrate at various concentrations. gamma-Secretase activity is quantified by measuring the production of Abeta peptides or other cleavage products using ELISA, mass spectrometry, or fluorescence-based methods. IC₅0 values are determined from dose-response curves.
|
| Cell Assay |
For in vitro cellular experiments, LY-411575 isomer 1 is tested in cell lines that express APP, such as HEK293 cells or neuronal cells. Cells are cultured in appropriate media and treated with various concentrations of the compound. Abeta production is measured in the culture supernatant using ELISA or other detection methods. The compound's effects on cell viability and Notch signaling are also assessed.
|
| Animal Protocol |
For in vivo animal experiments, LY-411575 isomer 1 can be administered to rodents via various routes, including oral gavage, intravenous injection, or intraperitoneal injection. The compound's efficacy can be evaluated in transgenic mouse models of Alzheimer's disease that overproduce Abeta. Typical dosing regimens may range from 0.1 to 10 mg/kg. Abeta levels in the brain and cerebrospinal fluid are measured as pharmacodynamic markers. Cognitive function and disease progression are also assessed.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of LY-411575 isomer 1 are not extensively detailed in the provided references. As a small molecule with a molecular weight of 479.48, it may have reasonable oral bioavailability and tissue distribution, including brain penetration. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism and excretion pathways remain to be fully characterized.
|
| Toxicity/Toxicokinetics |
Toxicological data for LY-411575 isomer 1 are limited, as it is primarily a research tool. As a gamma-secretase inhibitor, its toxicity would depend on the importance of gamma-secretase for normal cellular function, including Notch signaling. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
|
| References | |
| Additional Infomation |
LY-411575 isomer 1 is a research compound used to study gamma-secretase biology and Alzheimer's disease. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a potent gamma-secretase inhibitor with IC₅0 of 0.078 nM (membrane) and 0.082 nM (cell-based).
|
| Molecular Formula |
C26H23F2N3O4
|
|---|---|
| Molecular Weight |
479.4753
|
| Exact Mass |
479.166
|
| CAS # |
209984-58-7
|
| Related CAS # |
LY-411575;209984-57-6;LY-411575 (isomer 2);2070009-70-8;LY-411575 (isomer 3);2070009-28-6
|
| PubChem CID |
78357869
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.85
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
789
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@@H](C(=O)N[C@H]1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)[C@@H](C4=CC(=CC(=C4)F)F)O
|
| InChi Key |
ULSSJYNJIZWPSB-AETJINEWSA-N
|
| InChi Code |
InChI=1S/C26H23F2N3O4/c1-14(29-25(34)23(32)15-11-16(27)13-17(28)12-15)24(33)30-22-20-9-4-3-7-18(20)19-8-5-6-10-21(19)31(2)26(22)35/h3-14,22-23,32H,1-2H3,(H,29,34)(H,30,33)/t14-,22-,23+/m0/s1
|
| Chemical Name |
(2S)-2-[[(2R)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
