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Purity: ≥98%
WHI-P97 is a novel, rationally designed, and potent inhibitor of Janus kinase (JAK)-3 with an estimated Ki value of 0.09 μM in modeling studies and a measured IC50 value of 2.5 μM in EGFR kinase inhibition assays. Treatment of mast cells with WHI-P97 inhibited 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/FcepsilonRI crosslinking by >90% at low micromolar concentrations. WHI-P97 did not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal. WHI-P97 was very well tolerated in mice, with no signs of toxicity at dose levels ranging from 5 microg/kg to 50 mg/kg, and LD(10) was not reached at a 50 mg/kg dose level when administered as a single i. p. or i.v. bolus dose. Therapeutic WHI-P97 concentrations, which inhibit mast cell leukotriene synthesis in vitro, could easily be achieved in vivo after the i.v. or i.p. administration of a single nontoxic 40 mg/kg bolus dose of WHI-P97. Notably, WHI-P97 showed promising biological activity in a mouse model of allergic asthma at nontoxic dose levels. Treatment of ovalbumin-sensitized mice with WHI-P97 prevented the development of airway hyper-responsiveness to methacholine in a dose-dependent fashion. Furthermore, WHI-P97 inhibited the eosinophil recruitment to the airway lumen after the ovalbumin challenge in a dose-dependent fashion. Further development of WHI-P97 may therefore provide the basis for new and effective treatment as well as prevention programs for allergic asthma in clinical settings
| ln Vitro |
At low micromolar doses, WHI-P97 prevents >90% of 5-lipoxygenase (5-LO) translocation from the nucleoplasm to the nuclear membrane, which in turn prevents 5-LO-dependent leukotriene (LT) generation following IgE receptor/FcεRI crosslinking[1]. Significantly lessening the IgE/antigen-induced LTC4 release from mast cells is WHI-P97 (30 μM)[1].
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| ln Vivo |
When provided as a single ip or iv bolus dosage, WHI-P97 is very well tolerated in mice, showing no symptoms of toxicity at dose levels ranging from 5 μg/kg to 50 mg/kg. Additionally, when LD10 is reached at a 50 mg/kg dose level, it is not achieved[1]. WHI-P97 (i.v. injection; 40 mg/kg; single dose) in CD-1 mice has a 58.9-minute elimination half-life (t1/2) and a systemic clearance (CL) of 891 ml/h/kg; in BALB/c mice, the t1/2 is 84.2 minutes and the CL is 1513 ml/h/kg. In CD-1 mice, the AUC and Cmax values are 107.3 μM and 296.7 μM, respectively. Furthermore, in BALB/c mice, the IC50 values are 212.7 μM and 58.4 μM, respectively. In CD-1 mice, the huge volume of distribution is 322 ml/kg, but in BALB/c mice, it is 415 ml/kg [1]. In a dose-dependent manner, WHI-P97 (intraperitoneal injection; 40 mg/kg; 24 days) protects ovalbumin-sensitized mice from developing airway hyperresponsiveness to methacholine. In a dose-dependent manner, WHI-P97 prevents eosinophil recruitment to the airway lumen following the ovalbumin challenge[1].
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| Animal Protocol |
Animal/Disease Models: BALB/c mouse model of allergic asthma[1]
Doses: 40 mg/kg Route of Administration: intraperitoneal (ip)injection; 24 days Experimental Results: demonstrated promising biological activity in a mouse model of allergic asthma at nontoxic dose levels. |
| References |
[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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| Molecular Formula |
C16H13BR2N3O3
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| Molecular Weight |
455.11
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| CAS # |
211555-05-4
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| SMILES |
BrC1=CC(NC2=NC=NC3=CC(OC)=C(OC)C=C32)=CC(Br)=C1O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.59 mg/mL (1.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.9 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.59 mg/mL (1.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.9 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1973 mL | 10.9864 mL | 21.9727 mL | |
| 5 mM | 0.4395 mL | 2.1973 mL | 4.3945 mL | |
| 10 mM | 0.2197 mL | 1.0986 mL | 2.1973 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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