| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
| Targets |
Target: Elenbecestat targets BACE1 (beta-site APP cleaving enzyme 1), a key enzyme in the production of amyloid-β (Aβ) peptides. BACE1 cleaves amyloid precursor protein (APP) at the β-secretase site, initiating the production of Aβ peptides. By inhibiting BACE1 activity, Elenbecestat reduces cleavage of APP and subsequent production of Aβ40 and Aβ42 peptides. This prevents aggregation of Aβ into toxic oligomers and protofibrils that form amyloid plaques in the brain.
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|---|---|
| ln Vitro |
In Vitro Activity: Elenbecestat demonstrates potent BACE1 inhibitory activity in biochemical assays. It reduces Aβ production in cell-based models. Detailed IC50 values and specific in vitro activity data are available from the primary literature. The compound shows high potency against BACE1 with favorable selectivity over other aspartyl proteases. It effectively lowers Aβ40 and Aβ42 levels in cell culture supernatants in a concentration-dependent manner.
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| ln Vivo |
In Vivo Activity: Elenbecestat reduces plasma beta-amyloid levels after single dosing in preclinical models. It demonstrates brain penetration and central Aβ reduction. The compound has been evaluated in animal models of Alzheimer's disease. In clinical trials, Elenbecestat was investigated for the treatment of Alzheimer's disease. However, development was discontinued due to potential liver enzyme elevations and risk-benefit considerations.
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| Enzyme Assay |
In Vitro Enzyme/Receptor Binding Protocol: BACE1 enzymatic activity assays typically use recombinant BACE1 enzyme and a fluorogenic or luminescent peptide substrate based on the APP β-secretase cleavage site. Inhibition is measured by decreased substrate cleavage in the presence of varying concentrations of Elenbecestat. IC50 values are determined from dose-response curves. Selectivity assays against related aspartyl proteases such as BACE2, cathepsin D, and renin are performed to assess specificity.
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| Cell Assay |
In Vitro Cell-Based Assay Protocol: Cell-based assays using neuronal cell lines or primary neurons expressing APP are used to measure Aβ production. Cells are treated with Elenbecestat at various concentrations, and secreted Aβ40 and Aβ42 levels in conditioned media are measured by ELISA or immunoassay. Compound effect on cell viability is also assessed using standard cytotoxicity assays such as MTT or LDH release. Blood-brain barrier penetration can be assessed using in vitro BBB models.
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| Animal Protocol |
In Vivo Animal Assay Protocol: Transgenic mouse models of Alzheimer's disease (such as APP/PS1 or Tg2576 mice) are used for in vivo efficacy studies. Elenbecestat is administered orally, and plasma and brain Aβ levels are measured at various time points. Chronic dosing studies assess amyloid plaque burden and cognitive function using behavioral tests such as Morris water maze. Pharmacodynamic markers including Aβ levels in cerebrospinal fluid are measured.
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| ADME/Pharmacokinetics |
Pharmacokinetics: Elenbecestat is orally bioavailable and penetrates the blood-brain barrier. After oral administration, it reduces plasma Aβ levels. Detailed PK parameters including half-life, Cmax, and brain penetration have been characterized in preclinical and clinical studies. The compound's ability to cross the blood-brain barrier is essential for its central nervous system target engagement. Elimination pathways and metabolite profiles have been studied in the context of clinical development.
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| Toxicity/Toxicokinetics |
Toxicity: Elenbecestat was evaluated in clinical trials for Alzheimer's disease. However, elevated liver enzymes were observed in 2 patients, leading to the discontinuation of the trial in May 2018. The primary reason for discontinuation was the potential risk of liver toxicity. No other significant toxicity concerns were reported at therapeutic doses. Comprehensive toxicity data are available from clinical studies. The compound is for research use only and is not clinically approved.
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| References | |
| Additional Infomation |
Additional Information: Elenbecestat has CAS number 1388149-39-0, molecular formula C19H15F6N5O2S, and molecular weight 491.41. It is also known as E-2609, E2609, and E 2609. The compound is a BACE1 inhibitor with potential for Alzheimer's disease treatment. By inhibiting BACE, a key enzyme in Aβ peptide production, E2609 decreases formation of toxic oligomers and protofibrils that form amyloid plaques. Clinical development was discontinued due to liver enzyme elevation risk. For research use only, not for human therapy.
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| Molecular Weight |
491.410123109818
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|---|---|
| Exact Mass |
491.085
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| CAS # |
1388149-39-0
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| Related CAS # |
1388149-39-0;Elenbecestat HCl;
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| PubChem CID |
57524928
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
2.1
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
773
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
S1C(N)=N[C@@]2(C3C(=CC=C(C=3)NC(C3C=NC(C(F)F)=CN=3)=O)F)CO[C@H](C(F)(F)F)[C@H]2C1
|
| InChi Key |
ZKKFSFUYHYWFFE-FWVNDXEPSA-N
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| InChi Code |
InChI=1S/C19H15F6N5O2S/c20-11-2-1-8(29-16(31)13-5-27-12(4-28-13)15(21)22)3-9(11)18-7-32-14(19(23,24)25)10(18)6-33-17(26)30-18/h1-5,10,14-15H,6-7H2,(H2,26,30)(H,29,31)/t10-,14+,18-/m1/s1
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| Chemical Name |
N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide
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| Synonyms |
E-2609; E2609; E 2609.
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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 | 2.0350 mL | 10.1748 mL | 20.3496 mL | |
| 5 mM | 0.4070 mL | 2.0350 mL | 4.0699 mL | |
| 10 mM | 0.2035 mL | 1.0175 mL | 2.0350 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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