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.
For research use only. We do not sell to patients.
- CAS No.: 2365306-62-1
- Formula: C19H16Cl2F7N5O2
- Molecular Weight:550.26
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Umibecestat hydrochloride
MoreAll Cathepsin Isoforms
More
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
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| CHO | IC50 |
2.8 nM
|
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.
|
30224383 |
| CHO | IC50 |
44 nM
|
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.
|
30224383 |
| CHO | IC50 |
0.003 μM
|
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.
|
34648711 |
| CHO | IC50 |
0.004 μM
|
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.
|
34648711 |
| CHO | IC50 |
0.044 μM
|
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.
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.
-
Animal Model:Sprague Dawley (male, 3-4 months old, healthy normal model)[1]
-
Dosage:1.5 mg/kg; 15.4 mg/kg; 51.3 mg/kg
-
Administration:oral gavage; single dose
-
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.
-
Animal Model:Beagle (male, 4 months of age, healthy normal model)[1]
-
Dosage:3.1 mg/kg
-
Administration:oral gavage; single dose
-
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.
-
Animal Model:Sprague-Dawley rats (male, approximately 300 g body weight)[2]
-
Dosage:3 μmol/kg; 10 μmol/kg; 30 μmol/kg; 100 μmol/kg
-
Administration:p.o.; single dose
-
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.
-
Animal Model:Rat[3]
-
Dosage:200 mg/kg/day
-
Administration:daily; 6 months
-
Result:Significantly reduced brain Aβ levels.
Did not affect the length and organization of mossy fibers in the hippocampus.
Chemical Information
-
CAS No. 2365306-62-1
-
Molecular Weight 550.26
-
Formula C19H16Cl2F7N5O2
-
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
-
Synonyms
CNP520 hydrochloride
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (1)
-
Journal Impact Factor
-
Most Recent
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Umibecestat hydrochloride Related Classifications
HY-119689A Related Classifications
Powered by Bioz