Alvelestat (AZD9668)

製品コードS7218 バッチS721805

印刷

化学情報

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

C25H22F3N5O4S
分子量 545.53 CAS No. 848141-11-7
Solubility (25°C)* 体外 DMSO 100 mg/mL (183.3 mM)
Water Insoluble
Ethanol 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 Alvelestat (AZD9668, Avelestat) is an oral, highly selective inhibitor of neutrophil elastase (NE) with IC50 and Ki of 12 nM and 9.4 nM, at least 600-fold more selective over other serine proteases. Phase 2.
in vitro AZD9668 inhibits plasma NE activity in zymosan-stimulated whole blood, and also inhibits NE activity on the surface of stimulated polymorphonuclear cells and in the supernatant of primed, stimulated cells. [1]
in vivo In mice and rats, AZD9668 (p.o.) prevents human NE-induced lung injury. In a mouse model of smoke-induced airway inflammation, AZD9668 significantly reduces the number of BAL neutrophils and BAL IL-1β. In a guinea pig chronic smoke model, AZD9668 prevents airspace enlargement and small airway wall remodeling in guinea pigs in response to chronic tobacco smoke exposure. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Potency, Selectivity of AZD9668
The potency and selectivity of AZD9668 are determined by measuring the cleavage of peptide substrates to products by a range of serine proteases: human NE, Pr-3, catG, pancreatic elastase, trypsin, and chymotrypsin. Substrate concentrations are chosen to be at or below their calculated Km values. The final substrate concentrations are as follows: MeOSuc-Ala-Ala-Pro-Val 7-amido-4-methylcoumarin (100 μM); Boc-Ala-Ala-Nva-SBzl (60 μM); N-α-benzoyl-L-arginine 7-amido-4-methylcoumarin (150 μM); Suc-Ala-Ala-Pro-Phe 7-amido-4-methylcoumarin (200 μM); and Abz-Glu-Pro-Phe-Trp-Glu-Asp-Glu-EDDn (8 μM). Enzymes are preincubated with inhibitors for 15 min before the addition of substrate, and the amount of product is measured 90 min later (60 min for porcine pancreatic elastase) after the addition of a low-pH stopping buffer (acetate buffer, pH 4.3 containing 0.20 M sodium monochloroacetate, 0.06 M sodium acetate, and 0.14 M acetic acid). Potency (IC50) is defined as the molar concentration of AZD9668 required to inhibit protease activity by 50%. The Cheng-Prusoff equation is then used to calculate Ki using predetermined values for Km (data not shown): Ki = IC50/(1 + [S]/Km). A broader analysis of AZD9668 selectivity is made by an external company in more than 300 ligand-binding, enzyme, and ion-channel assays using a single concentration of AZD9668 (10 μM). Activity in these assays is flagged by ≥50% inhibition. Full IC50 determinations are then performed in assays where activity is observed.
動物実験 動物モデル Human NE-induced acute lung injury in mice or rats, guinea pig chronic smoke model.
投薬量 ~10 mg/kg (mice); ~20 mg/kg (rats); ~100 mg/kg (pigs)
投与方法 p.o.

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：

Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity [ Proc Natl Acad Sci U S A, 2021, 118(34)e2102435118] PubMed: 34353890
A Novel Supplementation Approach to Enhance Host Response to Sublingual Vaccination [ Sci Rep, 2019, 9(1):715] PubMed: 30679470
NETs promote ALI/ARDS inflammation by regulating alveolar macrophage polarization. [ Exp Cell Res, 2019, 382(2):111486] PubMed: 31255598
Inhibitors of elastase stimulate murine B lymphocyte differentiation into IgG‐and IgA‐producing cells [Attia Z Eur J Immunol, 2018, 48(8):1295-1301] PubMed: 29710424

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。