受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder | |
化学式 | C16H13Br2N3O3 |
|||
分子量 | 455.10 | CAS No. | 211555-05-4 | |
Solubility (25°C)* | 体外 | DMSO | 8 mg/mL (17.57 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. |
製品説明 | WHI-P97 is a potent inhibitor of JAK-3 with an estimated Ki value of 0.09 μM in modeling studies and a measured IC50 value of 2.5 μM in EGFR kinase inhibition assays. |
---|---|
in vitro | Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcεRI crosslinking by >90% at low micromolar concentrations. WHI-P97 does not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal[1]. |
in vivo | WHI-P97 was very well tolerated in mice, with no signs of toxicity at dose levels ranging from 5 μg/kg to 50 mg/kg, and LD10was not reached at a 50 mg/kg dose level when administered as a single i.p. or i.v. bolus dose. Therapeutic WHI-P97 concentrations, which inhibit mast cell leukotriene synthesis in vitro, could easily be achieved in vivo after the i.v. or i.p. administration of a single nontoxic 40 mg/kg bolus dose of WHI-P97. WHI-P97 showed promising biological activity in a mouse model of allergic asthma at nontoxic dose levels. Treatment of ovalbumin-sensitized mice with WHI-P97 prevented the development of airway hyper-responsiveness to methacholine in a dose-dependent fashion. WHI-P97 inhibited the eosinophil recruitment to the airway lumen after the ovalbumin challenge in a dose-dependent fashion. WHI-P97 had an elimination half-life (t1/2) of 58.9 min and systemic clearance (CL) of 891 ml/h/kg in CD-1 mice and a t1/2 of 84.2 min and CL of 1513 ml/h/kg in BALB/c mice. The values for AUC and Cmaxwere 107.3 μM·h and 296.7 μM, respectively, in CD-1 mice, and 58.4 μM·h and 212.7 μM, respectively, in BALB/c mice. The large volume of distribution [322 ml/kg in CD-1 mice and 415 ml/kg in BALB/c mice; ∼6-fold greater than the plasma volume (50 ml/kg)] suggests that WHI-P97 may be extensively partitioned into extravascular compartments[1]. |
細胞アッセイ | 細胞株 | RBL-2H3 cells |
---|---|---|
濃度 | 30 μM | |
反応時間 | 30 min | |
実験の流れ | RBL-2H3 cells were cultured overnight on 22- × 22-mm coverslips at a cell density of 0.01 × 106/ml with 0.24 mg/ml DNP-IgE. Sensitized RBL-2H3 cells were then treated with 30 μM WHI-P97, WHI-P131, or vehicle before challenge with 20 ng/ml DNP-BSA at 37°C. After stimulation with DNP-BSA, the cells were fixed in cold methanol for 30 min, permeabilized in cold acetone, and blocked with 1% BSA containing nonimmune goat serum. Staining of mast cells with primary and secondary antibodies followed by confocal laser scanning microscopy. |
|
動物実験 | 動物モデル | female CD-1 or male BALB/c mice |
投薬量 | 40 mg/kg | |
投与方法 | i.v. and i.p. |
Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model [ J Med Chem, 2020, 31] | PubMed: 32191458 |
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。