211555-05-4
基本信息
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
物理化學(xué)性質(zhì)
常見(jiàn)問(wèn)題列表
Target | Value |
JAK3
() |
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.
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. |