| Description | Lanabecestat (AZD3293) is a highly potent and highly permeable, orally active BACE1 inhibitor (Ki: 0.4 nM) that crosses the blood-brain barrier, Lanabecestat can be used for the study of neurological diseases like Alzheimer's disease. |
| In vitro | Lanabecestat 差异性地改变了 5xFAD 和 APP KI小鼠的小胶质细胞蛋白水平[1]。 |
| In vivo | Lanabecestat 治疗（1 mg/kg；口服灌胃；每天一次；持续 3 周）能在 4-AP 细胞发生模型中增加了 Bace1-null 小鼠的爆发频率[1]。 |
| Cell experiments | Cells are incubated with different Lanabecestat concentrations for 5 to 16?h, and the release of sAβPPβ, Aβ1-40, Aβ1-42, or sAβPPα into the medium is analyzed using kits. Cytotoxic effect of Lanabecestat is evaluated in the cell plates using cell proliferation/cytotoxicity kit. |
| Animal experiments | Female 7- to 14-week-old C57BL/6 mice (n=6 per treatment group and time point) receive a vehicle or Lanabecestat solution at 50, 100, or 200 μmol/kg (20, 41, or 82?mg/kg) as a single dose via oral gavage. Mice and guinea pigs are anesthetized 1.5, 2, 3, 4, 6, 8, 16, 24, or 48?h after the (last) administration of vehicle or drug and are then kept under isoflurane anesthesia. Cerebrospinal fluid (CSF) is aspirated from the cisterna magna, and plasma is isolated from blood collected by cardiac puncture into EDTA tubes. The animals are then sacrificed by decapitation, and the brains are dissected into hemispheres. |
| Target activity | BACE1:0.4 nM (cell free), BACE1:0.4 nM |
| Synonyms | LY3314814, AZD3293 |
| molecular weight | 412.53 |
| Molecular formula | C26H28N4O |
| CAS | 1383982-64-6 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 80 mg/mL (193.92 mM), Sonication is recommended. |
| References | 1. Yao AY, et al. Bace1 Deletion in the Adult Reverses Epileptiform Activity and Sleep-wake Disturbances in AD Mice. J Neurosci. 2023 Aug 30;43(35):6197-6211. 2. Eketjäll S, et al. AZD3293: A Novel, Orally Active BACE1 Inhibitor with High Potency and Permeability and Markedly Slow Off-Rate Kinetics. J Alzheimers Dis. 2016;50(4):1109-23. |