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211555-05-4

中文名稱 4-(3',5'-二溴-4-羥基苯基)氨基-6,7-二甲氧基喹唑啉
英文名稱 WHI-P97
CAS 211555-05-4
分子式 C16H13Br2N3O3
分子量 455.1
MOL 文件 211555-05-4.mol
更新日期 2024/12/03 15:40:35
211555-05-4 結(jié)構(gòu)式 211555-05-4 結(jié)構(gòu)式

基本信息

中文別名
4-(3',5'-二溴-4-羥基苯基)氨基-6,7-二甲氧基喹唑啉
英文別名
WHI-P-97
WHI P97
JAK3 Inhibitor I USP/EP/BP
2,6-dibromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol
Phenol, 2,6-dibromo-4-[(6,7-dimethoxy-4-quinazolinyl)amino]-
WHI-P 974-(3',5'-DibroMo-4-hydroxyphenyl)aMino-6,7-diMethoxyquinazoline
所屬類別
生物化工:蛋白酪氨酸激酶

物理化學(xué)性質(zhì)

沸點(diǎn)470.9±45.0 °C(Predicted)
密度1.785
儲(chǔ)存條件-20°C儲(chǔ)存
溶解度DMSO : 5.88 mg/mL (12.92 mM; Need ultrasonic)H2O : < 0.1 mg/mL (insoluble)
酸度系數(shù)(pKa)7.05±0.36(Predicted)
形態(tài)粉末
顏色White to gray

常見(jiàn)問(wèn)題列表

生物活性
WHI-P97是一種有效的JAK-3抑制劑,Ki值為0.09 μM,在EGFR激酶抑制試驗(yàn)中IC50為2.5 μM。
靶點(diǎn)
TargetValue
JAK3
()
體外研究

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.WHI-P97 (30 μM) stantially reduces the IgE/antigen-induced LTC4 release from mast cells.

體內(nèi)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 LD 10 is not reached at a 50 mg/kg dose level when administered as a single i.p. or i.v. bolus dose.WHI-P97 (i.v. injection; 40 mg/kg; single dose) has 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 C max are 107.3 μM and 296.7 μM, respectively, in CD-1 mice. And the IC 50 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.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.

Animal Model: BALB/c mouse model of allergic asthma
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.
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