| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
BACE-1[1]
Elenbecestat targets beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 is the enzyme responsible for the first cleavage of amyloid precursor protein (APP) in the production of amyloid-beta peptides. By inhibiting BACE1, Elenbecestat reduces the production of amyloid-beta, thereby decreasing amyloid plaque formation in the brain. This mechanism is a key strategy for the treatment of Alzheimer's disease. |
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| ln Vitro |
In a cell-based experiment, elenebecestat (E2609) has an IC50 of around 7 nmol/L, making it a strong BACE1 inhibitor[2]. It has been demonstrated that elenebecestat lowers the generation of Ab in rodent plasma, brain, and cerebrospinal fluid (CSF)[2].
In vitro, Elenbecestat is a potent BACE1 inhibitor with demonstrated activity in reducing amyloid-beta production. The compound shows high potency against BACE1 and is CNS-penetrant. Standard in vitro assays include enzyme activity assays using purified BACE1 and fluorogenic substrates, cell-based assays measuring Aβ production in APP-expressing cells, and selectivity profiling against other aspartyl proteases. The compound's IC50 for BACE1 inhibition is determined from dose-response curves. |
| ln Vivo |
Potently inhibiting the synthesis of Ab1-40 and Ab1-42 in the plasma and CSF of non-human primates is elenbecestat (E2609; 0.3-30 mg/kg; po)[2]. Following a single daily dosage, elenebecestat exhibits a plasma half-life of 12–16 hours[1].
In vivo, Elenbecestat demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing. The compound is orally bioavailable and CNS-penetrant, allowing it to reach the brain and inhibit BACE1 activity. It has been studied in clinical trials for Alzheimer's disease. However, clinical development has been discontinued due to lack of efficacy or safety concerns. The compound is for research use only and is used to study BACE1 inhibition in Alzheimer's disease. |
| Enzyme Assay |
For non-cell-based receptor binding assays, Elenbecestat can be evaluated using purified BACE1 enzyme. Enzyme activity assays are performed using a fluorogenic substrate that is cleaved by BACE1. Increasing concentrations of the test compound are added, and the rate of substrate cleavage is measured by fluorescence. IC50 values are calculated from the inhibition curves. Selectivity profiling is performed using related aspartyl proteases such as BACE2, cathepsin D, and renin to assess specificity.
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| Cell Assay |
For in vitro cellular assays, cells expressing amyloid precursor protein (APP) are cultured in appropriate media. Cells are treated with various concentrations of Elenbecestat, and Aβ production in the cell culture supernatant is measured using ELISA or immunoassay. The reduction in Aβ levels compared to control wells indicates BACE1 inhibitory activity. IC50 values for cellular Aβ reduction are calculated from dose-response curves. Cytotoxicity is assessed using MTT or LDH assays to ensure that observed effects are not due to cell death.
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| Animal Protocol |
Animal/Disease Models: Cynomolgus monkeys (pharmacokinetic/PK analysis)[2]
Doses: 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 30 mg/kg Route of Administration: Oral administration Experimental Results: Potently inhibits Ab1- 40 and Ab1-42 production in the plasma and CSF. For in vivo animal studies, Elenbecestat is typically administered orally to transgenic mouse models of Alzheimer's disease. Blood samples are collected at various time points post-administration for measurement of plasma Aβ levels. Brain tissue is collected for measurement of brain Aβ levels and BACE1 activity. Behavioral tests may be performed to assess cognitive function. Pharmacokinetic studies involve measuring compound concentrations in plasma and brain tissue. Dosing regimens vary depending on the specific model and study objectives. Clinical trials have been conducted in healthy subjects and Alzheimer's disease patients. |
| ADME/Pharmacokinetics |
Elenbecestat is an orally bioavailable compound with a molecular weight of 437.44 and a molecular formula of C19H18F3N5O2S. It is soluble in DMSO (78 mg/mL or 87 mg/mL) and ethanol (11 mg/mL). The compound demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing. It has been studied in multiple clinical trials, including Phase 1 and Phase 2 studies. However, clinical development has been discontinued. The compound is for research use only.
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| Toxicity/Toxicokinetics |
The toxicity profile of Elenbecestat has been evaluated in clinical trials. Common adverse effects may include those associated with BACE1 inhibition, such as effects on myelination and cognitive function. The compound's clinical development has been discontinued, potentially due to lack of efficacy or safety concerns. The compound is for research use only and not for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies, as well as assessment of effects on the central nervous system.
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| References | |
| Additional Infomation |
Elenbecestat is being investigated in the clinical trial NCT02956486 (a 24-month study designed to evaluate the efficacy and safety of Elenbecestat (E2609) in patients with early-stage Alzheimer's disease).
Elenbecestat (E2609) is a novel, potent, orally bioavailable BACE1 inhibitor for the treatment of Alzheimer's disease (AD). It demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing. The compound is CNS-penetrant and has been studied in clinical trials. However, clinical development has been discontinued. It is for research use only and is used to study BACE1 inhibition in Alzheimer's disease. |
| Molecular Formula |
C19H18F3N5O2S
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|---|---|
| Molecular Weight |
437.438732624054
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| Exact Mass |
437.113
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| CAS # |
1388651-30-6
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| PubChem CID |
57827330
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
687
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| Defined Atom Stereocenter Count |
3
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| 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)[C@H]2C1
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| InChi Key |
AACUJFVOHGRMTR-DPXNYUHVSA-N
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| InChi Code |
InChI=1S/C19H18F3N5O2S/c1-9-12-7-30-18(23)27-19(12,8-29-9)11-4-10(2-3-13(11)20)26-17(28)15-6-24-14(5-25-15)16(21)22/h2-6,9,12,16H,7-8H2,1H3,(H2,23,27)(H,26,28)/t9-,12-,19-/m1/s1
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| Chemical Name |
N-[3-[(4aS,5R,7aS)-2-amino-5-methyl-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-(difluoromethyl)pyrazine-2-carboxamide
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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) |
DMSO: ≥ 250 mg/mL (571.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2860 mL | 11.4301 mL | 22.8603 mL | |
| 5 mM | 0.4572 mL | 2.2860 mL | 4.5721 mL | |
| 10 mM | 0.2286 mL | 1.1430 mL | 2.2860 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02322021
Conditions:Alzheimer Disease|Dementia, Alzheimer TypeLink: https://clinicaltrials.gov/ct2/show/NCT02956486
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT02859207
Conditions:Early Alzheimer's Disease
Title:Study to Evaluate the Safety and Tolerability of a Once Daily Dose of 50 mg E2609 in Healthy Japanese Subjects
Status:Completed
updateDate:2017-04-18
Ctid:NCT03055962
Link: https://clinicaltrials.gov/ct2/show/NCT03055962
Conditions:Healthy ParticipantsLink: https://clinicaltrials.gov/ct2/show/NCT01600859
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT01975636
Conditions:Metabolism and EliminationLink: https://clinicaltrials.gov/ct2/show/NCT01511783
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT02055703
Conditions:Healthy SubjectsLink: https://clinicaltrials.gov/ct2/show/NCT02207790
Conditions:Healthy SubjectsLink: https://clinicaltrials.gov/ct2/show/NCT02222324
Conditions:Healthy SubjectsLink: https://clinicaltrials.gov/ct2/show/NCT01716897
Conditions:Alzheimer's DiseaseProducts are for research use only; We do not sell to patients
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