| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
LY-411575 (isomer 3) targets the gamma-secretase complex, an intramembrane protease responsible for the final cleavage of APP to generate amyloid-beta (Abeta) peptides. It is a potent inhibitor with an IC50 of 0.078 nM in membrane-based assays and 0.082 nM in cell-based assays. It also potently inhibits Notch cleavage with an IC50 of 0.41 nM.
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| ln Vitro |
In cell-free membrane assays, LY-411575 (isomer 3) inhibits gamma-secretase activity with an IC50 of 0.078 nM. In vitro, it blocks the production of Abeta peptides from APP and also inhibits the cleavage of Notch, a key developmental signaling protein, with an IC50 of 0.41 nM. This dual activity is critical for validating target engagement.
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| ln Vivo |
In vivo, LY-411575 (isomer 3) is used to block gamma-secretase activity in animal models. By inhibiting the enzyme, it dramatically lowers brain Abeta levels. However, due to its potent inhibition of Notch signaling, its in vivo use is often limited to short-term studies to avoid severe mechanism-based toxicities associated with chronic Notch blockade.
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| Enzyme Assay |
Cell-free membrane assays are performed using membrane preparations rich in gamma-secretase. The membranes are incubated with a recombinant APP-C100-flag substrate and varying concentrations of LY-411575 (isomer 3). After incubation, the reaction products are analyzed by ELISA for Abeta40 to determine the half-maximal inhibitory concentration (IC50).
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| Cell Assay |
Cellular assays are conducted in neuroglioma H4 cells stably overexpressing APP. Cells are seeded in 96-well plates and treated with a dilution series of LY-411575 (isomer 3) for 16-24 hours. The conditioned medium is collected, and Abeta40 levels are quantified using a specific sandwich ELISA to calculate the IC50 for cellular inhibition of gamma-secretase.
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| Animal Protocol |
In vivo studies are conducted in transgenic mouse models of Alzheimer‘s disease (e.g., Tg2576). Mice receive a single oral dose or intraperitoneal injection of LY-411575 (isomer 3). After a predetermined time (e.g., 3-6 hours), the animals are sacrificed. Brain tissue is harvested, and the levels of Abeta40 and Abeta42 are extracted and quantified by ELISA to assess the degree of gamma-secretase inhibition.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) profile of LY-411575 (isomer 3) shows that it is cell-permeable and reaches the brain. Following administration, the compound achieves rapid and dose-dependent central nervous system (CNS) exposure, leading to a profound and rapid reduction in brain Abeta levels in preclinical species.
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| Toxicity/Toxicokinetics |
Due to its potent inhibition of Notch cleavage, the primary toxicological concern for LY-411575 (isomer 3) is mechanism-based toxicity. Chronic inhibition of Notch can cause severe gastrointestinal toxicity, including goblet cell metaplasia and intestinal bleeding. Its in vivo use is therefore typically limited to acute or sub-chronic studies.
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| References | |
| Additional Infomation |
LY-411575 (isomer 3) is the active enantiomer of LY411575, a benchmark gamma-secretase inhibitor. Its molecular formula is C26H23F2N3O4 and its molecular weight is 479.48. This isomer is the most active form and is a critical tool for studying gamma-secretase biology and the validation of amyloidogenic pathways as drug targets for Alzheimer‘s disease. It is for research use only.
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| Exact Mass |
479.166
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|---|---|
| CAS # |
2070009-28-6
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| Related CAS # |
LY-411575;209984-57-6;LY-411575 isomer 1;209984-58-7;LY-411575 (isomer 2);2070009-70-8
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| PubChem CID |
78357871
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
789
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| Defined Atom Stereocenter Count |
3
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| 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
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| InChi Key |
ULSSJYNJIZWPSB-JRVVOHRXSA-N
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| 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-/m1/s1
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| Chemical Name |
(2R)-2-[[(2R)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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.) |
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
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