Umibecestat hydrochloride
Based on 1 publication(s) in Google Scholar
Umibecestat hydrochloride (CNP520 hydrochloride) 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 hydrochloride reduces β-Amyloid levels in the brain and cerebrospinal fluid, decreases β-amyloid plaque deposition, and inhibits plaque-associated neuroinflammation. Umibecestat hydrochloride is used in research related to Alzheimer's disease.
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- CAS. Nr.: 2365306-62-1
- Formel: C19H16Cl2F7N5O2
- Molecular Weight:550.26
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications Citing Use of MedChemExpress (MCE) Umibecestat hydrochloride
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Biologische Aktivität
Beschreibung
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 |
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| CHO | IC50 |
2.8 nM
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Inhibition of Aβ40 release from wild-type APP-transfected CHO cells in an amyloid-β release inhibition assay.
Inhibition of Aβ40 release from wild-type APP-transfected CHO cells in an amyloid-β release inhibition assay.
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30224383 |
| CHO | IC50 |
44 nM
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Inhibition of Aβ40 release from Swedish mutant APP-transfected CHO cells in an amyloid-β release inhibition assay.
Inhibition of Aβ40 release from Swedish mutant APP-transfected CHO cells in an amyloid-β release inhibition assay.
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30224383 |
| CHO | IC50 |
0.003 μM
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Inhibition of hAβ40 production in wild-type human APP751 stably transfected CHO (wtAPP-CHO) cells in a cellular Aβ release inhibition assay.
Inhibition of hAβ40 production in wild-type human APP751 stably transfected CHO (wtAPP-CHO) cells in a cellular Aβ release inhibition assay.
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34648711 |
| CHO | IC50 |
0.004 μM
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Inhibition of sAPPβ production in wild-type human APP751 stably transfected CHO (wtAPP-CHO) cells in a cellular Aβ release inhibition assay.
Inhibition of sAPPβ production in wild-type human APP751 stably transfected CHO (wtAPP-CHO) cells in a cellular Aβ release inhibition assay.
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34648711 |
| CHO | IC50 |
0.044 μM
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Inhibition of hAβ40 production in Swedish mutant APP stably transfected CHO (SweAPP-CHO) cells in a cellular Aβ release inhibition assay.
Inhibition of hAβ40 production in Swedish mutant APP stably transfected CHO (SweAPP-CHO) cells in a cellular Aβ release inhibition assay.
|
34648711 |
In Vitro
Umibecestat hydrochloride 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 hydrochloride effectively inhibits Aβ40 secretion in CHO cells transfected with wild-type and Swedish mutant APP[1].
Umibecestat hydrochloride inhibits the hERG potassium channel in in vitro assays, with an IC50 of 3.2 μM[1].
Umibecestat hydrochloride (10 mM; 0.5-30 min) exhibits good in vitro metabolic stability in liver microsomes[2].
Umibecestat hydrochloride 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. Further protocols information, click here.
In Vivo
Following a single oral administration of Umibecestat hydrochloride 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 hydrochloride 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.
Chemical Information
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CAS. Nr. 2365306-62-1
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Molecular Weight 550.26
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Formel C19H16Cl2F7N5O2
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SMILES
C[C@@]1(N=C([C@@](C)(OC1)C(F)(F)F)N)C2=C(F)C=CC(NC(C3=C(C=C(C=N3)C(F)(F)F)Cl)=O)=N2.Cl
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Synonyms
CNP520 hydrochloride
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (1)
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Journal Impact Factor
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Most Recent
Protokoll
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Neurological Diseases
PINK1/Parkin-mediated mitophagy pathway is a mitochondrial quality-control signaling axis in which mitochondrial depolarization stabilizes PINK1 on damaged mitochondria, activates Parkin recruitment and E3 ubiquitin ligase activity, promotes ubiquitination of outer mitochondrial membrane proteins, recruits selective autophagy adaptors, and drives lysosomal degradation of damaged mitochondria. In neurological disease research, this pathway is experimentally important because neurons, especially dopaminergic neurons, are highly dependent on mitochondrial integrity, and defective mitochondrial turnover can lead to mitochondrial dysfunction, oxidative stress, impaired neuronal survival, α-synuclein accumulation, and neuroinflammatory damage-associated signals. The genetic disease link is strongest in Parkinson’s disease because mutations in PRKN/parkin cause autosomal recessive juvenile parkinsonism, mutations in PINK1 cause hereditary early-onset Parkinson’s disease, and Drosophila studie
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)