Verubecestat
Based on 5 publication(s) in Google Scholar
Verubecestat (MK-8931) is an orally active, high-affinity BACE1 and BACE2 inhibitor with Ki values of 2.2 nM and 0.38 nM. Verubecestat effectively reduces Aβ40 and has the potential for Alzheimer's Disease.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 99.56%
- CAS. Nr.: 1286770-55-5
- Formel: C17H17F2N5O3S
- Molecular Weight:409.41
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Chemical Information
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Publications Citing Use of MedChemExpress (MCE) Verubecestat
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Biologische Aktivität
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BACE1 |
BACE2 |
Verubecestat (MK-8931) is a β-site amyloid precursor protein cleaving enzyme 1/2 (BACE1/2) inhibitor. Verubecestat does not significantly inhibit human CYP isoforms 1A2, 2C9, 2C19, 2D6, and 3A4 (all IC50>40 μM), indicating that the compound is unlikely to be a perpetrator of CYP-mediated drug-drug interactions[1].
Verubecestat has IC50s of 2.1 nM, 0.7 nM, 4.4 nM for Aβ1-40, Aβ1-42, sAPPβ in HEK293 APPSwe/Lon cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Verubecestat (1 mg/kg; IV) has a T1/2 of 4.9 hours, a CL of 21 mL/min/kg, a Vss of 7.5 L/kg for cynomolgus monkeys[1].
Verubecestat (1 mg/kg; IV) has a T1/2 of 9.7 hours, a CL of 4.3 mL/min/kg, a Vss of 2.7 L/kg for beagle dogs[1].
Verubecestat (30 mg/kg; orally; BID for 5 days) causes a modest (1.4-fold) induction of CYP 3A1 activity but does not significantly alter the expression of CYPs 1A1, 1A2, 2B, 3A2, or 4A in rats[1].
Verubecestat dose-dependently reduces CSF and cortex Aβ40 with ED50 values of 5 and 8 mg/kg, respectively, corresponding to unbound plasma EC50 values of 48 and 81 nM, respectively[1].
Verubecestat (3 and 10 mg/kg; orally) reduces profound, sustained of CSF Aβ40 levels and has peak effects on CSF Aβ lowering (72 and 81% reduction at 3 and 10 mg/kg, respectively) 12 h after dosing[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (SD) rats[1]
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Dosage:3 mg/kg (Pharmacokinetic Analysis)
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Administration:IV or oral
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Result:Had a T1/2 of 1.9 hours, a CL of 46 mL/min/kg, a Vss of 5.4 L/kg, a Cmax of 0.27 μM and a AUC of 1.1 μM•h.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS. Nr. 1286770-55-5
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Appearance Solid
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Molecular Weight 409.41
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Formel C17H17F2N5O3S
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Color White to off-white
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SMILES
O=C(C1=NC=C(F)C=C1)NC2=CC=C(F)C([C@@](C3)(C)N=C(N)N(C)S3(=O)=O)=C2
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Synonyms
MK-8931
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (5)
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Journal Impact Factor
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Most Recent
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Cell Death Differ
CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer's disease. [Abstract]2022 Dec;29(12):2417-2428. PMID: 35732922 -
Microorganisms
In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase. [Abstract]2023 Jun 18;11(6):1608. PMID: 37375110 -
Cytokine
Shedding new light on BACE1-mediated modulation of IL-6 signaling: Implications for neural activity and synaptic plasticity in mice. [Abstract]2025 Apr 3:190:156925. PMID: 40184913 -
Front Biosci (Landmark Ed)
2024 Feb 21;29(2):78. PMID: 38420818 -
Lösungsmittel & Löslichkeit
DMSO : ≥ 35 mg/mL (85.49 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Reinheit & Dokumentation
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Data Sheet (277 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Scott JD, et al. Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer'sDisease. Med Chem. 2016 Dec 8;59(23):10435-10450. [Content Brief]
[2]. Yan R, et al. Stepping closer to treating Alzheimer's disease patients with BACE1 inhibitor drugs. Transl Neurodegener. 2016 Jul 14;5:13. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4425 mL | 12.2127 mL | 24.4254 mL | 61.0635 mL |
| 5 mM | 0.4885 mL | 2.4425 mL | 4.8851 mL | 12.2127 mL | |
| 10 mM | 0.2443 mL | 1.2213 mL | 2.4425 mL | 6.1063 mL | |
| 15 mM | 0.1628 mL | 0.8142 mL | 1.6284 mL | 4.0709 mL | |
| 20 mM | 0.1221 mL | 0.6106 mL | 1.2213 mL | 3.0532 mL | |
| 25 mM | 0.0977 mL | 0.4885 mL | 0.9770 mL | 2.4425 mL | |
| 30 mM | 0.0814 mL | 0.4071 mL | 0.8142 mL | 2.0354 mL | |
| 40 mM | 0.0611 mL | 0.3053 mL | 0.6106 mL | 1.5266 mL | |
| 50 mM | 0.0489 mL | 0.2443 mL | 0.4885 mL | 1.2213 mL | |
| 60 mM | 0.0407 mL | 0.2035 mL | 0.4071 mL | 1.0177 mL | |
| 80 mM | 0.0305 mL | 0.1527 mL | 0.3053 mL | 0.7633 mL |
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