Umibecestat
Based on 1 publication(s) in Google Scholar
Umibecestat (CNP520) is a selective, orally active BACE inhibitor, with an IC50 of 11 nM for hBACE-1, 10 nM for mouse BACE-1, and 30 nM for hBACE-2. Umibecestat reduces β-Amyloid levels in the brain and cerebrospinal fluid, decreases β-amyloid plaque deposition, and inhibits plaque-associated neuroinflammation. Umibecestat is used in research related to Alzheimer's disease.
For research use only. We do not sell to patients.
- Purity : 99.81%
- CAS No.: 1387560-01-1
- Formula: C19H15ClF7N5O2
- Molecular Weight:513.80
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) Umibecestat
MoreAll Cathepsin Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
BACE1 11 nM (IC50) |
BACE2 30 nM (IC50) |
Cathepsin D 205000 nM (IC50) |
Cathepsin E 66400 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | IC50 |
3 nM
Compound: 5; CNP-520
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Inhibition of BACE1 in CHO cells expressing human APP assessed as reduction in amyloidbeta (1 to 40 residues) level incubated for 24 hrs by immunoassay method
Inhibition of BACE1 in CHO cells expressing human APP assessed as reduction in amyloidbeta (1 to 40 residues) level incubated for 24 hrs by immunoassay method
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[PMID: 30709653] |
In Vitro
Umibecestat is a potent inhibitor of hBACE-1, with a selectivity for BACE-1 that is more than 20000-fold higher than its selectivity for h-Cathepsin D[1].
Umibecestat effectively inhibits Aβ40 secretion in CHO cells transfected with wild-type and Swedish mutant APP[1].
Umibecestat inhibits the hERG potassium channel in in vitro assays, with an IC50 of 3.2 μM[1].
Umibecestat (10 mM; 0.5-30 min) exhibits good in vitro metabolic stability in liver microsomes[2].
Umibecestat is a potent inhibitor of Aβ and sAPPβ release in wild-type APP-overexpressing CHO cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Following a single oral administration of Umibecestat at a dose of 3.1 mg/kg in beagle dogs, Aβ40 and Aβ42 levels in the cerebrospinal fluid decrease continuously by more than 75% within 12-48 hours, and the compound exhibits high central nervous system distribution efficiency[1].
Umibecestat (3-100 μmol/kg; oral; single dose) hydrochloride produces a dose-dependent reduction in Aβ40 in Sprague-Dawley rats, and the reduction of cerebral Aβ40 reaches 89.1% 4 h after administration at an oral dose of 100 μmol/kg[2].
Umibecestat (200 mg/kg/day; administered daily for 6 months) hydrochloride significantly reduces Aβ levels in the rat brain without altering the histological structure of hippocampal mossy fibers[3].
Umibecestat reduces key pathological features of Alzheimer's disease in APP transgenic mouse models of Alzheimer's disease, including amyloid plaque burden and associated neuroinflammatory markers[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague Dawley (male, 3-4 months old, healthy normal model)[1]
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Dosage:1.5 mg/kg; 15.4 mg/kg; 51.3 mg/kg
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Administration:oral gavage; single dose
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Result:Reduced brain Aβ40 by 89.3% relative to untreated controls at 51.3 mg/kg dose.
Achieved oral ED50 of 2.4 mg/kg for 50% lowering of rat brain Aβ40.
Produced ~50% Aβ40 reduction in both rat brain and CSF at 24 hours post-dose following a 15.4 mg/kg single dose, with overlapping effect-over-time curves for brain and CSF demonstrating that Aβ pharmacodynamics in CSF mirrors that in brain tissue.
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Animal Model:Beagle (male, 4 months of age, healthy normal model)[1]
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Dosage:3.1 mg/kg
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Administration:oral gavage; single dose
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Result:Maintained detectable levels in blood for 192 hours and in CSF for 72 hours after dosing.
Achieved a ratio of unbound CNP520 in CSF to unbound CNP520 in blood of 0.7, demonstrating efficient distribution to the central nervous system.
Induced >75% reduction in both CSF Aβ40 and Aβ42 concentrations at 12-48 hours after dosing, with levels returning slowly to baseline over the following 7 days.
Yielded an in vivo IC50 of 103.1 nM for total CNP520 and 3.3 nM for unbound CNP520 in dog blood via PK/PD modeling.
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Animal Model:Sprague-Dawley rats (male, approximately 300 g body weight)[2]
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Dosage:3 μmol/kg; 10 μmol/kg; 30 μmol/kg; 100 μmol/kg
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Administration:p.o.; single dose
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Result:Reach blood concentrations of 0.16 μM, 0.44 μM, 1.71 μM, and 3.43 μM at 3, 10, 30, and 100 μmol/kg doses respectively at 4 hours post-dose.
Reach corresponding brain concentrations of 0.18 μM, 0.85 μM, 3.28 μM, and 11.6 μM, with unbound brain concentrations of 0.002 μM, 0.008 μM, 0.03 μM, and 0.12 μM at 4 hours post-dose.
Achieve unbound brain concentration relative to the BACE1 IC50 of 0.18, 0.72, 3, and 11 at 3, 10, 30, and 100 μmol/kg doses respectively at 4 hours post-dose.
Produce brain Aβ40 reductions of 35.6%, 63.0%, 81.4%, and 89.1% at 3, 10, 30, and 100 μmol/kg doses respectively at 4 hours post-dose.
Produce corresponding CSF Aβ40 reductions of 59.3% (at 10 μmol/kg) and 78.2% (at 30 μmol/kg) at 4 hours post-dose.
Keep levels of the amide hydrolysis metabolite 21 in blood and brain all below 3.4% of parent compound levels at 4 hours post-dose.
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Animal Model:Rat[3]
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Dosage:200 mg/kg/day
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Administration:daily; 6 months
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Result:Significantly reduced brain Aβ levels.
Did not affect the length and organization of mossy fibers in the hippocampus.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1387560-01-1
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Appearance Solid
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Molecular Weight 513.80
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Formula C19H15ClF7N5O2
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Color White to off-white
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SMILES
O=C(NC1=NC([C@@]2(CO[C@](C)(C(N)=N2)C(F)(F)F)C)=C(C=C1)F)C3=NC=C(C=C3Cl)C(F)(F)F
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Synonyms
CNP520
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Publications (1)
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Journal Impact Factor
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Most Recent
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (194.63 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9463 mL | 9.7314 mL | 19.4628 mL | 48.6571 mL |
| 5 mM | 0.3893 mL | 1.9463 mL | 3.8926 mL | 9.7314 mL | |
| 10 mM | 0.1946 mL | 0.9731 mL | 1.9463 mL | 4.8657 mL | |
| 15 mM | 0.1298 mL | 0.6488 mL | 1.2975 mL | 3.2438 mL | |
| 20 mM | 0.0973 mL | 0.4866 mL | 0.9731 mL | 2.4329 mL | |
| 25 mM | 0.0779 mL | 0.3893 mL | 0.7785 mL | 1.9463 mL | |
| 30 mM | 0.0649 mL | 0.3244 mL | 0.6488 mL | 1.6219 mL | |
| 40 mM | 0.0487 mL | 0.2433 mL | 0.4866 mL | 1.2164 mL | |
| 50 mM | 0.0389 mL | 0.1946 mL | 0.3893 mL | 0.9731 mL | |
| 60 mM | 0.0324 mL | 0.1622 mL | 0.3244 mL | 0.8110 mL | |
| 80 mM | 0.0243 mL | 0.1216 mL | 0.2433 mL | 0.6082 mL | |
| 100 mM | 0.0195 mL | 0.0973 mL | 0.1946 mL | 0.4866 mL |
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