Lanabecestat (AZD3293)

製品コードS8193 バッチS819301

印刷

化学情報

Chemical Structure Synonyms LY3314814 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H28N4O
分子量 412.53 CAS No. 1383982-64-6
Solubility (25°C)* 体外 DMSO 82 mg/mL (198.77 mM)
Ethanol 82 mg/mL (198.77 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Lanabecestat (AZD3293, LY3314814) is an oral beta-secretase 1 cleaving enzyme (BACE) inhibitor.
in vitro Lanabecestat（AZD3293, LY3314814）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[1].
in vivo In 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[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 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)
濃度 --
反応時間 5 to 16 h
実験の流れ

The cells 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.
動物実験 動物モデル C57BL/6 mice
投薬量 50, 100, or 200μmol/kg
投与方法 oral administration

カスタマーフィードバック

Data from [Data independently produced by , , Anal Bioanal Chem, 2017, 409(28):6635-6642]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A study of protein-drug interaction based on solvent-induced protein aggregation by fluorescence correlation spectroscopy [ Analyst, 2022, 10.1039/d2an00031h] PubMed: 35253833
Partial Reduction of Amyloid β Production by β-Secretase Inhibitors Does Not Decrease Synaptic Transmission [ Alzheimers Res Ther, 2020, 26;12(1):63] PubMed: 32456694
Multiple proteases are involved in mesothelin shedding by cancer cells [ Commun Biol, 2020, 3(1):728] PubMed: 33262421
Multiple BACE1 inhibitors abnormally increase the BACE1 protein level in neurons by prolonging its half-life. [ Alzheimers Dement, 2019, 15(9):1183-1194] PubMed: 31416794
A cellular complex of BACE1 and γ-secretase sequentially generates Aβ from its full-length precursor. [ J Cell Biol, 2019, 218(2):644-663] PubMed: 30626721
A microfluidics-based mobility shift assay to identify new inhibitors of β-secretase for Alzheimer's disease [Liu R, et al. Anal Bioanal Chem, 2017, 409(28):6635-6642] PubMed: 28889204

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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