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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Atabecestat (formerly known as JNJ-54861911) is a novel potent, oral, and brain-penetrant BACE1 inhibitor that inhibits β-site amyloid precursor protein cleaving enzyme 1 (BACE1), an enzyme up-regulated in Alzheimer's disease. β-Secretase enzyme (BACE) inhibition has been proposed as a priority treatment mechanism for Alzheimer's 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.
| Targets |
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) [1]
- β-site amyloid precursor protein cleaving enzyme 1 (BACE1) [2] |
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| ln Vitro |
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| 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 young and elderly healthy participants who received single and multiple ascending doses of Atabecestat (JNJ-54861911) (up to 14 days), plasma Aβ, CSF Aβ, and CSF-sAPPβ were reduced in a dose-dependent manner, with the maximum Aβ reduction reaching up to 95%. The Aβ reduction effect outlasted the exposure to Atabecestat (JNJ-54861911). APOE ε4 carrier status and baseline Aβ levels did not influence the reductions in Aβ or sAPPβ [1] - In plaque-depositing mice (including transgenic mice) treated with a combination of Atabecestat (JNJ-54861911) (chronic BACE1 inhibitor treatment) and a novel high-affinity antibody against 3pE-modified Aβ, significant clearance of pre-existing amyloid deposits in the brain was achieved without induction of microhemorrhages or other histopathological findings [2] |
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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. Plaque-depositing mouse model (including transgenic mice) for combination therapy efficacy study: Mice with established plaque deposition were subjected to chronic treatment with Atabecestat (JNJ-54861911) combined with a novel antibody against 3pE-modified Aβ. The specific drug formulation, dissolution method, administration frequency, and route were not provided in the literature. The study evaluated the effect of the combination therapy on amyloid deposit clearance and histopathological changes (such as microhemorrhages) [2] |
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| ADME/Pharmacokinetics |
Atabecestat (JNJ-54861911) exhibited dose-proportional pharmacokinetic characteristics in cerebrospinal fluid and plasma after single and multiple administrations in healthy subjects [1].
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| Toxicity/Toxicokinetics |
Atabecestat (JNJ-54861911) was well tolerated in healthy subjects with rare, drug-independent adverse events [1] - Atabecestat (JNJ-54861911) in combination with a 3pE-specific antibody did not induce microbleeds or other histopathological toxicities in mice with plaque deposition [2]
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| References |
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| Additional Infomation |
Atabecestat is being investigated in the clinical trial NCT02211079 (a study evaluating the pharmacokinetic effects of a mixture of cytochrome P450 (CYP) 3A4, CYP2B6, CYP2C9 and CYP1A2 substrates, represented by JNJ-54861911).
Atabecestat (JNJ-54861911) is a potent oral BACE1 inhibitor that can cross the blood-brain barrier[1] - The imbalance between the production and clearance of amyloid-β peptide (Aβ) and its accumulation in the brain is an early and crucial step in the pathogenesis of Alzheimer's disease (AD), and Atabecestat (JNJ-54861911) targets this process by inhibiting BACE1 to prevent the de novo production of Aβ[2] - Two randomized, placebo-controlled, double-blind studies were conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of atabecestat (JNJ-54861911) in young and older healthy subjects, with blood and cerebrospinal fluid samples collected periodically (up to 36 hours after the last dose) for analysis[1]. - Research disease-modifying therapies for Alzheimer's disease (AD) include reducing brain Aβ concentrations through BACE1 inhibitors (such as atabestat (JNJ-54861911)) and clearing Aβ deposits through passive Aβ immunotherapy; the combined use of these two methods may improve treatment efficacy and bring good safety [2]. |
| Molecular Formula |
C18H14FN5OS
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| Molecular Weight |
367.400064945221
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| Exact Mass |
367.09
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| CAS # |
1200493-78-2
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| Related CAS # |
1200493-78-2;Atabecestat HCl;
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| PubChem CID |
68254185
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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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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
659
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| Defined Atom Stereocenter Count |
1
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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 |
VLLFGVHGKLDDLW-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C18H14FN5OS/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)/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 | 2.7218 mL | 13.6091 mL | 27.2183 mL | |
| 5 mM | 0.5444 mL | 2.7218 mL | 5.4437 mL | |
| 10 mM | 0.2722 mL | 1.3609 mL | 2.7218 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03587376 | COMPLETED | Drug: Atabecestat | Alzheimer Disease | Janssen Research & Development, LLC | 2018-05-30 | Early Phase 1 |
| NCT02569398 | TERMINATEDWITH RESULTS | Drug: Atabecestat, 5 mg Drug: Atabecestat, 25 mg Drug: Placebo |
Asymptomatic Amyloid-positive | Janssen Research & Development, LLC | 2015-10-29 | Phase 2 Phase 3 |
 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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