WHI-P97

SKU: orb1225685

Description

A potent, specific JAK3 inhibitor with Ki of 0.6-2.3 uM; inhibits the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and inhibits mast cell leukotriene synthesis in vitro; shows promising biological activity in mouse model of allergic asthma.

Key Properties

• CAS Number: 211555-05-4
• MW: 455.1007
• Purity: >98% (HPLC)
• Formula: C₁₆H₁₃Br₂N₃O₃
• SMILES: OC1=C(Br)C=C(NC2=C3C=C(OC)C(OC)=CC3=NC=N2)C=C1Br
• Target: JAK
• Solubility: 10 mM in DMSO

Bioactivity

• 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 LD10 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 (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. 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

WHI-P-97 | WHI P97

Quick Database Links

Gene Symbol

JAK