| Description | BACE1-IN-5 (Compound 15), a potent β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, demonstrates significant efficacy with an IC50 of 9.1 nM for BACE1 inhibition and an impressive IC50 of 0.82 nM against cellular amyloid-β (Aβ) production. Additionally, it is engineered to enhance hERG inhibition and P-gp efflux, indicating its optimized medicinal chemistry profile [1]. |
| In vivo | BACE1-IN-5 (Compound 15; 1-3 mg/kg; oral administration; for 2-6 hours; male ICR mice) treatment causes a significant and dose-dependent decrease of total Aβ, reduces total Aβ by 76% (4 hours) at a free brain concentration of 4.1 ng/mL (8.9 nM) at 1 mg/kg. BACE1-IN-5 demonstrats a K p,uu value of 1.3 at 1 mg/kg (4 hours time point). At 3 mg/kg, a maximum Aβ reduction of 87% is achieved at a free brain concentration of 9.5 ng/mL (21 nM) [1]. Animal Model: Male ICR mice [1] Dosage: 1 mg/kg, 3 mg/kg Administration: Oral administration; for 2 hours, 4 hours, and 6 hours Result: A significant and dose-dependent decrease of total Aβ was seen, reduced total Aβ by 76% (4 h) at a free brain concentration of 4.1 ng/mL (8.9 nM) at 1 mg/kg. Demonstrats a K p,uu value close to 1 (K p,uu of 1.3) at 1 mg/kg (4 h time point). At 3 mg/kg, a maximum Aβ reduction of 87% was achieved at a free brain concentration of 9.5 ng/mL (21 nM). |
| Target activity | BACE1:9.1 nM , Cellular β-Amyloid:0.82 nM |
| molecular weight | 461.41 |
| Molecular formula | C18H16F5N5O2S |
| CAS | 2581114-83-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Kusakabe KI, et al. Trifluoromethyl Dihydrothiazine-Based β-Secretase (BACE1) Inhibitors with Robust Central Aβ Reduction and Minimal Covalent Binding Burden. ChemMedChem. 2019 Oct 27. |