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Purity: ≥98%
| Targets |
Atabecestat targets β-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as β-secretase. BACE1 is the enzyme responsible for the first cleavage of amyloid precursor protein (APP), initiating the production of amyloid-beta (Aβ) peptides. Aβ aggregation and deposition in the brain are key pathological features of Alzheimer's disease. By inhibiting BACE1, Atabecestat reduces Aβ production, potentially slowing cognitive decline.
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| ln Vitro |
Atabecestat (formerly known as JNJ-54861911) is a novel potent, oral, and brain-penetrant inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), which is an enzyme that is up-regulated in Alzheimer’s disease. β-Secretase enzyme (BACE) inhibition has been proposed as a priority treatment mechanism for Alzheimers disease (AD), but treatment initiation may need to be very early. JNJ-54861911 was found to inhibit BACE1 with approximately 2,600 nM affinity to 1 nM affinity. JNJ-54861911 was well-tolerated, adverse events were uncommon and unrelated to JNJ-54861911. JNJ-54861911 showed dose-proportional CSF and plasma pharmacokinetic profiles.
Kinase Assay: JNJ-54861911 inhibited BACE1 with IC50 of 2,600 nM to 1 nM. In vitro, Atabecestat is a potent BACE1 inhibitor. It is brain-penetrant and achieves robust reduction of Aβ levels. Specific IC50 values for BACE1 inhibition are not detailed in the available sources. The compound's activity has been characterized in enzymatic assays measuring BACE1-mediated cleavage of APP substrates. Cellular activity has been assessed in neuronal cell cultures by measuring Aβ production. |
| ln Vivo |
Mice treated with atabecestat (100 and 300 mg/kg; po once daily for 3 days) have lower levels of human Aβ[2]. When APPPS1 mice are treated with 3D6, atabecestat (300 mg/kg; po once) prevents the vascular abnormalities from getting worse[2].
In vivo, Atabecestat is orally active and brain-permeable, achieving robust and high CSF Aβ reduction. It has been evaluated in clinical trials for the potential treatment of Alzheimer's disease. The compound has been shown to slow cognitive decline in participants with preclinical Alzheimer's disease. Specific animal model data are not detailed in the available sources. |
| Enzyme Assay |
The BACE1 inhibition assay for Atabecestat involves incubating the compound with recombinant BACE1 enzyme and a fluorogenic peptide substrate that mimics the APP β-secretase cleavage site. The reaction is carried out in a BACE1 assay buffer at 37°C for a specified time. The cleavage of the substrate releases a fluorophore, and the fluorescence is measured using a microplate reader. IC50 values are calculated from dose-response curves.
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| Cell Assay |
To evaluate the cellular activity of Atabecestat, neuronal cell lines or primary neurons are seeded in 96-well plates and treated with varying concentrations of Atabecestat. After incubation, the levels of Aβ peptides (Aβ40 and Aβ42) in the cell culture supernatant are measured using ELISA. The EC50 for reduction of Aβ production is calculated. Cell viability is monitored using an MTT or LDH assay to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
Animal/Disease Models: 5weeks old APPPS1 mice[2]
Doses: 100 and 300 mg/kg Route of Administration: po (oral gavage); 100 and 300 mg/kg; one time/day for 3 days Experimental Results: decreased the level of human Aβ1- 40 and Aβ1-42 levels in the brain of APPPS1 mice at a dose of 300 mg/kg and resulted in less reduction of human Aβ levels at 24 h with a dose of 100 mg/kg. The in vivo efficacy of Atabecestat is evaluated in transgenic mouse models of Alzheimer's disease (such as APP/PS1 mice). Mice are administered Atabecestat orally at various doses for a specified period. At the end of the treatment period, animals are euthanized, and brain tissue and CSF are collected. Aβ levels in brain homogenates and CSF are measured by ELISA. The compound's ability to reduce brain Aβ levels is expressed as the percentage reduction compared to vehicle-treated controls. Cognitive function can be assessed using behavioral tests such as the Morris water maze. |
| ADME/Pharmacokinetics |
Atabecestat is characterized as being orally active and brain-permeable. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular formula of C18H15FN6OS and a molecular weight of 382.42. It is a small molecule with properties suitable for oral administration and central nervous system penetration.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Atabecestat are not provided in the available sources. The compound has been evaluated in clinical trials for Alzheimer's disease, indicating that its safety profile has been assessed in humans. As a BACE1 inhibitor, its potential toxicity may be related to off-target effects on other enzymes or to the physiological role of BACE1 in other tissues. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
Atabecestat is also known as JNJ-54861911. It is an orally active and brain-permeable inhibitor of BACE1 that achieves robust and high CSF Aβ reduction. It has been developed for the potential treatment of Alzheimer's disease and has been shown to slow cognitive decline in participants with preclinical Alzheimer's disease.
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| Molecular Formula |
C18H15CLFN5OS
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| Molecular Weight |
403.86
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| Exact Mass |
367.09
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| Elemental Analysis |
C, 53.53; H, 3.74; Cl, 8.78; F, 4.70; N, 17.34; O, 3.96; S, 7.94
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| CAS # |
1200493-78-2
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| Related CAS # |
1200493-78-2;Atabecestat HCl;
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.681
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| LogP |
1.63
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| SMILES |
S1C(N)=N[C@](C=C1)(C)C1C(=CC=C(C=1)NC(C1C=CC(C#N)=CN=1)=O)F
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| InChi Key |
JUWYQYLCONMVPW-FERBBOLQSA-N
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| InChi Code |
InChI=1S/C18H14FN5OS.ClH/c1-18(6-7-26-17(21)24-18)13-8-12(3-4-14(13)19)23-16(25)15-5-2-11(9-20)10-22-15;/h2-8,10H,1H3,(H2,21,24)(H,23,25);1H/t18-;/m0./s1
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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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 | 2.4761 mL | 12.3805 mL | 24.7611 mL | |
| 5 mM | 0.4952 mL | 2.4761 mL | 4.9522 mL | |
| 10 mM | 0.2476 mL | 1.2381 mL | 2.4761 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.
 Stable reduction in Aβ species (Aβ1–42, Aβ1–40, Aβ1–38, Aβ1–37) in CSF compared to baseline as measured 14–15days after repeated dosing with 90-mgJNJ-54861911.Alzheimers Dement (N Y).2016 Aug 24;2(3):202-212. |
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 CSF sAPPα increase and sAPPβ decrease in the MAD study as measured 14–15days after repeated dosing with JNJ-54861911.Alzheimers Dement (N Y).2016 Aug 24;2(3):202-212. |
 APOEε4 carrier status has no impact on Aβ or sAPPβ reduction.Alzheimers Dement (N Y).2016 Aug 24;2(3):202-212. |
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