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AZD3293(Lanabecestat)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AZD3293(Lanabecestat)图片
CAS NO:1383982-64-6
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)412.53
FormulaC26H28N4O
CAS No.1383982-64-6 (free base);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 82 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: 82 mg/mL (198.8 mM)
Solubility (In vivo) Lanabecestat; LY3314814; AZD3293; LY-3314814; AZD-3293; LY 3314814; AZD 3293
Synonyms NC(C(C)=N1)=NC21C3=C(C=CC(C4=CC(C#CC)=CN=C4)=C3)C[C@@]52CC[C@@H](OC)CC5
实验参考方法
In Vitro

In vitro activity: AZD3293 is a potent, highly permeable, orally active, blood-brain barrier (BBB) penetrating, BACE1 inhibitor with unique slow off-rate kinetics. When the potency of AZD3293 with respect to secretion of Aβ40 and sAβPPβ is studied in a range of cellular models, the compound 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). AZD3293 is also tested in a panel of more than 350 in vitro radioligand binding and enzyme activity assays, covering a diverse range of receptors, ion channels, transporters, kinases, and enzymes, up to a concentration of 10μM of AZD3293. A few significant responses are observed, but these had at least a 1,000-fold selectivity against BACE1, thus indicating specificity to BACE1. The off-rate of AZD3293 has an estimated t1/2 of approximately 9 h.


Kinase Assay: Lanabecestat (formerly known as AZD3293 and LY3314814), is a novel potent, orally bioactive, highly permeable, brain-penetreable inhibitor of beta-secretase 1 cleaving enzyme (BACE) with a Ki of 0.4 nM. AZD3293 displayed significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ.


Cell Assay: The cells [SH-SY5Y, SH-SY5Y overexpressing wild type AβPP, HEK293 cells overexpressing AβPP with the Swedish mutation (K595N/M596L), N2A cells, and primary cortical neurons isolated from fetal C57BL/6 mice (E16) or Dunkin-Hartley guinea pigs (E25-27)] are incubated with different AZD3293 concentrations for 5 to 16 h, and the release of sAβPPβ, Aβ1-40, Aβ1-42, or sAβPPα into the medium is analyzed using specific commercial ELISA or kits from Meso Scale Discovery.

In VivoIn vivo in mice, guinea pigs, and dogs, AZD3293 displays significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ. In the dog PK study, the bioavailability of AZD3293 is determined to be 80% (F = 0.8). The preclinical data strongly support the clinical development of AZD3293, and patients with AD are currently being recruited into a combined Phase 2/3 study to test the disease-modifying properties of AZD3293.
Animal modelC57BL/6 mice
Formulation & DosageFormulated in 5% dimethylacetamide in 0.3 M gluconic acid, pH 3; 50, 100, or 200μmol/kg; p.o.
ReferencesJ Alzheimers Dis. 2016;50(4):1109-23.