WHI-P97 是一种有效的选择性 JAK-3 抑制剂。WH

WHI-P97

WHI-P97 是一种有效的选择性 JAK-3 抑制剂。WHI-P97 在动物模型中有效预防过敏性哮喘的发展。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
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生物活性    
WHI-P97 is a potent and selective JAK-3 inhibitor. WHI-P97 is effective in preventing the development allergic asthma in vivo[1].

IC50 & Target[1]    
JAK3
11 μM (IC50)

体外研究
WHI-P97 inhibits 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[1].
WHI-P97 (30 μM) stantially reduces the IgE/antigen-induced LTC4 release from mast cells[1].

体内研究
WHI-P97 is very well tolerated in mice, with no signs of toxicity at dose levels ranging from 5 μg/kg to 50 mg/kg, and LD10 is not reached at a 50 mg/kg dose level when administered as a single i.p. or i.v. bolus dose[1].
WHI-P97 (i.v. injection; 40 mg/kg; single dose) has 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 Cmax are 107.3 μM and 296.7 μM, respectively, in CD-1 mice. And the IC50 values are 58.4 μM and 212.7 μM, respectively, in BALB/c mice. The large volume of distribution are 322 ml/kg in CD-1 mice and 415 ml/kg in BALB/c mice[1].
WHI-P97 (intraperitoneal injection; 40 mg/kg; 24 days) prevents ovalbumin-sensitized mice the development of airway hyper-responsiveness to methacholine in a dose-dependent fashion in mice. WHI-P97 inhibits the eosinophil recruitment to the airway lumen after the ovalbumin challenge in a dose-dependent fashion[1].

Animal Model:    BALB/c mouse model of allergic asthma[1]
Dosage:    40 mg/kg
Administration:    intraperitoneal injection; 24 days
Result:    Showed promising biological activity in a mouse model of allergic asthma at nontoxic dose levels.

分子量    
455.10

性状    
Solid

Formula    
C16H13Br2N3O3

CAS 号    
211555-05-4

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 3.33 mg/mL (7.32 mM; ultrasonic and warming and heat to 80°C)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.1973 mL    10.9866 mL    21.9732 mL
5 mM    0.4395 mL    2.1973 mL    4.3946 mL
10 mM    ---    ---    ---
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 0.59 mg/mL (1.30 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 0.59 mg/mL (1.30 mM); Clear solution

 

参考文献	[1]. R Malaviya, et al. Treatment of allergic asthma by targeting janus kinase 3-dependent leukotriene synthesis in mast cells with 4-(3', 5'-dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97). J Pharmacol Exp Ther. 2000 Dec;295(3):912-26.  [Content Brief]