MedChemExpress LLC (MCE)

MedChemExpress - Model Lanabecestat - 1383982-64-6

Lanabecestat (AZD3293) is a potent, orally active and blood-brain barrier penetrating BACE1 inhibitor with a Ki of 0.4 nM. Lanabecestat is used for the research of Alzheimer's disease[1].

Lanabecestat

MCE China：Lanabecestat

Brand：MedChemExpress (MCE)

Cat. No.HY-100740

CAS：1383982-64-6

Synonyms：AZD3293; LY3314814

Purity：99.67%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Lanabecestat (AZD3293) is a potent, orally active and blood-brain barrier penetrating BACE1 inhibitor with a Ki of 0.4 nM. Lanabecestat is used for the research of Alzheimer's disease.

In Vitro：Lanabecestat acts as a full inhibitor of BACE1 in vitro, with a competitive and reversible mechanism of action towards the hBACE1 active site. Lanabecestat displays a very high target affinity and a markedly slow target off-rate. The off-rate of lanabecestat has an estimated t1/2 of approximately 9?h. Lanabecestat displays pM potency in primary neuron cultures from mice and guinea pigs and in SH-SY5Y cells over-expressing AβPP (IC50=610 pM, 310 pM, and 80 pM, respectively). The in vitro plasma protein binding of lanabecestat is determined by equilibrium dialysis using mouse, rat, guinea pig, dog, and human plasma. The compound is stable in the plasma of these species for at least the duration of the in vitro incubation period. The unbound fractions are 1.3% to 1.8% for mice, 4.2% to 5.9% for rats, 8.3% to 10.3% for guinea pigs, 9.4% to 10.3% for dogs, and 7.7% to 9.4% for human plasma. The mean blood:plasma ratio of 0.7 in human blood indicates no significant association with red blood cells. The free fraction in the brain tissue binding assay is 4.5%[1].

In Vivo：In mice, guinea pigs, and dogs, lanabecestat displays significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ[1].

Animal Administration：Female 7- to 14-week-old C57BL/6 mice (n=6 per treatment group and timepoint) receive 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. 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[1].

Cell Assay：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[1].

IC50 & Target：BACE1

References：

[1]. 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. [Content Brief]

Brand introduction:
•   MCE (MedChemExpress) has a global exclusive compound library of more than 200 kinds, and we are committed to providing the most comprehensive range of high-quality small molecule active compounds for scientific research customers around the world；
•   More than 50,000 highly selective inhibitors and agonists are involved in various popular signaling pathways and disease areas；
•   The products cover a variety of recombinant proteins, peptides, commonly used kits, more PROTAC, ADC and other characteristic products, widely used in new drug research and development, life science and other scientific research projects；
•   Provide virtual screening, ion channel screening, metabolomics analysis detection analysis, drug screening and other professional technical services；
•   It has a professional experimental center and strict quality control and verification system；
•   Provide LC/MS, NMR, HPLC, chiral analysis, elemental analysis and other quality inspection reports to ensure the high purity and high quality of products；
•   The biological activity of the products has been verified by the experiments of customers in various countries；
•   A variety of top journals such as Nature, Cell, Science and pharmaceutical patents have included the scientific research results of MCE customers；
•   Our professional team tracks the latest pharmaceutical and life science research and provides you with the latest active compounds in the world；
•   It has established long-term cooperation with the world's major pharmaceutical companies and well-known scientific research institutions。