WHI-P97
WHI-P97 Basic information
- Product Name:
- WHI-P97
- Synonyms:
-
- WHI-P 974-(3',5'-DibroMo-4-hydroxyphenyl)aMino-6,7-diMethoxyquinazoline
- 2,6-dibromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol
- WHI-P-97;WHI P97
- Phenol, 2,6-dibromo-4-[(6,7-dimethoxy-4-quinazolinyl)amino]-
- JAK3 Inhibitor I USP/EP/BP
- WHI-P97
- Janus kinase,JAK,airway,Inhibitor,WHIP97,eosinophil recruitment,WHI-P97,inhibit,ovalbumin challenge,WHI P97,ovalbumin-sensitized,WHI-P-97
- CAS:
- 211555-05-4
- MF:
- C16H13Br2N3O3
- MW:
- 455.1
- Mol File:
- 211555-05-4.mol
WHI-P97 Chemical Properties
- Boiling point:
- 470.9±45.0 °C(Predicted)
- Density
- 1.785
- storage temp.
- Store at -20°C
- solubility
- DMSO : 5.88 mg/mL (12.92 mM; Need ultrasonic)H2O : < 0.1 mg/mL (insoluble)
- form
- Powder
- pka
- 7.05±0.36(Predicted)
- color
- White to gray
WHI-P97 Usage And Synthesis
Definition
ChEBI: 2,6-dibromo-4-[(6,7-dimethoxy-4-quinazolinyl)amino]phenol is a member of quinazolines.
Biological Activity
WHI-P97 is a potent JAK-3 inhibitor with Ki of 0.09 μM and IC50 of 2.5 μM in EGFR kinase inhibition assay.
in vitro
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.
in vivo
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 ip or iv bolus dose. WHI-P97 (iv 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 at 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 airwa y 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. |