| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(-)-FRM-024 targets gamma secretase, a transmembrane protease complex that cleaves the amyloid precursor protein (APP) to generate amyloid-beta (Abeta) peptides, which aggregate to form the amyloid plaques characteristic of Alzheimer‘s disease. As a modulator, it alters gamma secretase activity without completely inhibiting it, shifting the cleavage site to reduce the production of the toxic Abeta42 peptide while maintaining the production of shorter, less toxic Abeta species. This approach aims to reduce amyloid pathology while preserving normal Notch signaling.
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| ln Vitro |
Specific in vitro activity data for (-)-FRM-024 is not provided. As a potent gamma secretase modulator (GSM) and the active enantiomer of FRM-024, it is expected to potently reduce Abeta42 production in cell-based assays. GSMs typically have IC50 values in the low nanomolar range for reducing Abeta42, with minimal effects on Notch processing. The CNS-penetrant property ensures activity in neuronal cells.
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| ln Vivo |
Specific in vivo activity data for (-)-FRM-024 is not provided. As a CNS-penetrant gamma secretase modulator and the active enantiomer of the preclinical candidate FRM-024, it is expected to reduce brain Abeta42 levels in animal models of Alzheimer's disease. In transgenic mouse models (e.g., APP/PS1 or 5xFAD mice), chronic administration of a GSM would be expected to lower amyloid plaque burden, reduce neuroinflammation, and improve cognitive function.
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| Enzyme Assay |
The activity of (-)-FRM-024 as a gamma secretase modulator can be assessed using a cell-free gamma secretase activity assay. Procedure: Gamma secretase complex is immunoprecipitated from HEK293 cell lysates using an anti-presenilin antibody. The immunoprecipitate is incubated with a recombinant APP substrate (C100-Flag) and varying concentrations of (-)-FRM-024 (0.1-1000 nM) in assay buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 5 mM MgCl2, 1% CHAPSO) for 4 hours at 37degC. The reaction products (Abeta40 and Abeta42) are quantified by ELISA. The IC50 for Abeta42 reduction is calculated.
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| Cell Assay |
A cellular gamma secretase activity assay is performed in HEK293 cells expressing APP. Procedure: HEK293 cells stably expressing human APP (e.g., HEK293-APP cells) are seeded in 96-well plates (2×10⁴ cells/well) and allowed to attach overnight. Cells are treated with varying concentrations of (-)-FRM-024 (0.1-1000 nM) for 18-24 hours. Culture supernatants are collected, and Abeta40 and Abeta42 levels are measured using commercial ELISA kits (e.g., Wako). Cell viability is assessed by MTT assay. Notch processing is assessed by Western blotting of cell lysates using an anti-Notch intracellular domain (NICD) antibody. The ratio of Abeta42/Abeta40 is calculated. A reduction in the Abeta42/Abeta40 ratio with no change in NICD indicates specific GSM activity.
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| Animal Protocol |
In vivo efficacy can be evaluated in a mouse model of Alzheimer‘s disease (5xFAD or APP/PS1 mice). Procedure: Female 5xFAD mice (4 months old, n=10 per group) are administered (-)-FRM-024 orally at doses of 3, 10, and 30 mg/kg once daily for 8 weeks. Control groups receive vehicle or the GSM BMS-932481 (10 mg/kg). At the end of the study, mice are euthanized, and brains are collected. Soluble Abeta40 and Abeta42 levels in brain homogenates are measured by ELISA. Amyloid plaque burden is assessed by immunohistochemistry (6E10 antibody). Cognitive function is evaluated using the Morris water maze and Y-maze tests. Neuroinflammation markers (Iba-1, GFAP) are also assessed.
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| ADME/Pharmacokinetics |
A specific PK profile for (-)-FRM-024 is not provided. As a CNS-penetrant compound, it is expected to cross the blood-brain barrier and achieve high brain-to-plasma ratios. Oral administration is indicated based on the description of FRM-024 as a preclinical candidate. The compound is likely to have a half-life suitable for once-daily dosing. (-)-FRM-024 is the active enantiomer, and its PK may differ from the racemic mixture.
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| Toxicity/Toxicokinetics |
Specific toxicology data for (-)-FRM-024 is not available. Gamma secretase modulators (GSMs) are designed to avoid the Notch-related toxicities observed with full gamma secretase inhibitors (e.g., gastrointestinal toxicity and alterations in lymphocyte development). GSMs have a better safety profile, but long-term safety studies would be required. Standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
(-)-FRM-024 (l-FRM-024) is the active (-)-enantiomer of FRM-024, a CNS-penetrant gamma secretase modulator (GSM) developed for the treatment of Alzheimer‘s disease. Unlike gamma secretase inhibitors, which block Notch signaling and cause severe toxicity, GSMs shift the cleavage site of APP to reduce the production of the highly amyloidogenic Abeta42 peptide while preserving Notch processing. FRM-024 has been identified as a preclinical candidate for familial Alzheimer's disease. This product is for research use only and is not an approved drug.
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| Molecular Formula |
C22H22CLN5O2
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| Molecular Weight |
423.90
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| CAS # |
2085780-85-2
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| Appearance |
Typically exists as solids at room temperature
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3590 mL | 11.7952 mL | 23.5905 mL | |
| 5 mM | 0.4718 mL | 2.3590 mL | 4.7181 mL | |
| 10 mM | 0.2359 mL | 1.1795 mL | 2.3590 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.
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