WHI-P97

• CAT Number: I002627
• CAS Number: 211555-05-4
• Molecular Formula: C16H13Br2N3O3
• Molecular Weight: 455.10
• Purity: ≥95%
• Synonyms: 2,6-dibromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol
• InChI: InChI=1S/C16H13Br2N3O3/c1-23-13-5-9-12(6-14(13)24-2)19-7-20-16(9)21-8-3-10(17)15(22)11(18)4-8/h3-7,22H,1-2H3,(H,19,20,21)
• InChIKey: YVCXQRVVNQMZEI-UHFFFAOYSA-N
• SMILES: COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C(=C3)Br)O)Br)OC

WHI-P97 is a potent and selective JAK-3 inhibitor. WHI-P97 is effective in preventing the development allergic asthma in vivo[1].
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].
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].

Reference

[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.
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