Lanabecestat (AZD3293)

製品コードS8193 バッチS819302

印刷

化学情報

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

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	4.100mg/ml (9.94mM)	Taking the 1 mL working solution as an example, add 50 μL of 82 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.025mg/ml (2.48mM)	Taking the 1 mL working solution as an example, add 50 μL of 20.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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 this compound with respect to secretion of Aβ40 and sAβPPβ is studied in a range of cellular models, it 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). It 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. 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 t_1/2 of approximately 9 h^[1].
in vivo	In vivo studies in mice, guinea pigs, and dogs demonstrated that Lanabecestat (AZD3293) produces significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ. In the dog PK study, its bioavailability was determined to be 80% (F = 0.8). The preclinical data strongly support the clinical development of this compound, and patients with AD are currently being recruited into a combined Phase 2/3 study to test its disease-modifying properties^[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	After incubation with different concentrations of Lanabecestat (AZD3293) for 5 to 16 h, 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

参考

https://pubmed.ncbi.nlm.nih.gov/26890753/

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。