| Description |
Umibecestat (CNP520) is a beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibitor with IC50s of 11 nM and 10 nM for human BACE-1 and mouse BACE-1, respectively[1].
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| Related Catalog |
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| Target |
IC50: 11 nM (human BACE-1), 10 nM (mouse BACE-1)[1]
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| In Vitro |
Umibecestat is a potent BACE-1 inhibitor that is selective for BACE-1 over other human pepsin-like aspartic proteases, including BACE-2 and cathepsin D[1].
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| In Vivo |
Umibecestat (1.5-51.3 mg/kg; given by oral gavage; 72 hours) shows a dose-dependent effects on Aβ40 and a long duration of action in both rat brain and CSF[1]. Umibecestat (3.1 mg/kg; oral administration; 7 days) shows a > 75% reduction on Aβ40 and Aβ42 in CSF after dosing and returns slowly to baseline over the next 7 days[1]. Animal Model: Male rats (3-4 months old)[1] Dosage: 1.5 mg/kg (3 μM/kg)-51.3 mg/kg (100 μM/kg) Administration: Given by oral gavage; 72 hours Result: Reduced 89.3±4.5% Aβ40 at the highest dose in brain tissue, and 50% lowering of rat brain Aβ40 (ED50) was 2.4±0.31 mg/kg. Reduced ~50% Aβ40 at a single oral 30 μM/kg (15.4 mg/kg) dose after 24 hours in both rat brain and CSF。 Animal Model: 3-month-old beagle dogs[1] Dosage: 3.1 mg/kg (6 μM/kg) Administration: Oral administration; 7 days Result: Both Aβ40 and Aβ42 concentrations in CSF showed a > 75% reduction at 12-48 h after dosing and returned slowly to baseline over the next 7 days.
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| References |
[1]. Neumann U, et al. The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease. EMBO Mol Med. 2018 Nov;10(11). pii: e9316.
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