WHI-P97

製品コードS5904 バッチS590401

印刷

化学情報

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

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.

* <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	WHI-P97は、モデリング研究において推定Ki値0.09 μM、EGFRキナーゼ阻害アッセイにおいて測定IC50値2.5 μMを示す、JAK-3の強力な阻害剤です。
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. This compound does not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal.
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 concentrations of this compound, 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. It showed promising biological activity in a mouse model of allergic asthma at nontoxic dose levels. Treatment of ovalbumin-sensitized mice with this chemical prevented the development of airway hyper-responsiveness to methacholine in a dose-dependent fashion. It inhibited the eosinophil recruitment to the airway lumen after the ovalbumin challenge in a dose-dependent fashion. This compound had an elimination half-life (t_1/2) of 58.9 min and systemic clearance (CL) of 891 ml/h/kg in CD-1 mice and a t_1/2 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 it may be extensively partitioned into extravascular compartments.

プロトコル(参考用のみ)

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, this compound, 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.

参考

https://pubmed.ncbi.nlm.nih.gov/11082424/

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：

Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model [ J Med Chem, 2020, 31]	PubMed: 32191458

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。