| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
WHI-P180 (also known as Janex 3) is a multi-kinase inhibitor which inhibits RET, KDR and EGFR with IC50s of 5 nM, 66 nM and 4 μM, respectively. WHI-P180 is a potent in vitro and in vivo inhibitor of IgE-mediated mast cell responses. Additional preclinical research on WHI-P180 could enhance its in vivo efficacy and serve as a foundation for the development of efficient mast cell-mediated allergy reaction treatment and prevention initiatives. After being administered intravenously, intraperitoneally, or topically, WHI-P180 had an elimination half-life of less than 10 minutes in CD-1 (BALB/c) mice. WHI-P180 had a systemic clearance of 8188 mL/h/kg in BALB/c mice and 6742 mL/h/kg in CD-I mice. Interestingly, WHI-P180 inhibited IgE/antigen-induced vascular hyperpermeability in a well-characterized murine model of passive cutaneous anaphylaxis when given in two consecutive nontoxic intraperitoneal bolus doses of 25 mg/kg.
| Targets |
EGFR (IC50 = 4 μM); KDR (IC50 = 66 nM); RET (IC50 = 5 nM)
|
|---|---|
| ln Vitro |
WHI-P180 is also a potent inhibitor of mast cell responses mediated by IgE. WHI-P180 has an elimination half-life of less than ten minutes in CD-1 (BALB/c) mice after intravenous, intraperitoneal, or po administration. In CD-I mice, the systemic clearance of WHI-P180 is 6742 mL/h/kg, whereas in BALB/c mice, it is 8188 mL/h/kg. Interestingly, in a well-established murine model of passive cutaneous anaphylaxis, WHI-P180 inhibits IgE/antigen-induced vascular hyperpermeability when given in two consecutive nontoxic intraperitoneal bolus doses of 25 mg/kg[3].
|
| ln Vivo |
WHI-P180 is also a potent inhibitor of mast cell responses mediated by IgE. In CD-1 mice (BALB/c mice), the elimination half-life of WHI-P180 is less than 10 minutes following intravenous, intraperitoneal, or po injection. For CD-I mice, the systemic clearance rate of WHI-P180 was 6742 mL/h/kg, but for BALB/c mice, it was 8188 mL/h/kg. Notably, WHI-P180, when given as two consecutive intraperitoneal nontoxic bolus doses of 25 mg/kg, decreased IgE/antigen-induced vascular permeability in a well-characterized mouse model of passive cutaneous allergy. excessive sexuality [3].
|
| Enzyme Assay |
For fifteen minutes, inhibitors (WHI-P180) are pre-incubated in the plate containing five microliters of kinase and assay buffer at concentrations of thirteen pM RET and one hundred pM KDR. 5 μL of ATP and substrate added at 2×final reaction concentrations start the reaction. This is 18 μM and 2 μM for RET and 16 μM and 1 μM for KDR, respectively. At ATP Km, reactions are carried out for every target. After 20 minutes of assaying at room temperature, 10 μL of HTRF detection buffer supplemented with TK-antibody labelled with Eu3+-Cryptate (1:100 dilution) and streptavidin-XL665 (128 nM) is added to end the experiment. The FRET signal is measured after a one-hour incubation period at room temperature[1].
|
| Cell Assay |
A recombinant kinase that is activated is expressed by BaF3 cells that are dependent on IL3. Recombinant kinase activity is necessary for the survival and proliferation of the altered cells after IL3 is removed. In RPMI-1640 medium supplemented with 10% FBS and suitable antibiotics, BaF3 cell lines that express KIF5B-RET and KDR are raised. Recombinant mouse IL-3 (10 ng/mL) is added to 10% FBS-containing RPMI-1640 medium to sustain unmodified BaF3 cells (WT). An acoustic liquid handling platform is used to dispense compounds after cells are plated into 384-well plates at a density of 1500 or 3000 per well in 30 μL culture medium in order to determine the compound IC50. The viability of the cells is assessed by adding 10 μL of CellTiter-Glo reagent and measuring luminescence after they have been incubated for 48 hours at 37 °C in a humidified 5% CO2 atmosphere[1].
|
| Animal Protocol |
Mice: The measurement of mouse plasma WHI-P180 levels is done using a quantitative detection method based on high performance liquid chromatography (HPLC). The WinNonlin program is used to compute the pharmacokinetic parameters in order to fit the plasma concentration-time data to a single compartment pharmacokinetic model. The pharmacodynamic effects of WHI-P180 on vascular hyperpermeability associated with anaphylaxis are investigated using a cutaneous anaphylaxis model[3].
|
| References |
[1]. Newton R, et al. The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity. Eur J Med Chem. 2016 Apr 13;112:20-32.
[2]. Ghosh S, et al. 4-[3-Bromo-4-hydroxyphenyl)amino]-6,7-dimethoxyquinazolin-1-ium chloride methanol solvateand 4-[(3-hydroxyphenyl)amino]-6,7-dimethoxy-1-quinazolinium chloride. Acta Crystallogr C. 2001 Jan;57(Pt 1):76-8. [3]. Chen CL, et al. Pharmacokinetics and biologic activity of the novel mast cell inhibitor, 4-(3-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline in mice. Pharm Res. 1999 Jan;16(1):117-22 |
| Molecular Formula |
C16H15N3O3
|
|
|---|---|---|
| Molecular Weight |
297.31
|
|
| Exact Mass |
297.11
|
|
| Elemental Analysis |
C, 64.64; H, 5.09; N, 14.13; O, 16.14
|
|
| CAS # |
211555-08-7
|
|
| Related CAS # |
WHI-P180 hydrochloride;153437-55-9
|
|
| Appearance |
Solid powder
|
|
| SMILES |
COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)O)OC
|
|
| InChi Key |
BNDYIYYKEIXHNK-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C16H15N3O3/c1-21-14-7-12-13(8-15(14)22-2)17-9-18-16(12)19-10-4-3-5-11(20)6-10/h3-9,20H,1-2H3,(H,17,18,19)
|
|
| Chemical Name |
3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.41 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (8.41 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 10 mg/mL (33.63 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3635 mL | 16.8175 mL | 33.6349 mL | |
| 5 mM | 0.6727 mL | 3.3635 mL | 6.7270 mL | |
| 10 mM | 0.3363 mL | 1.6817 mL | 3.3635 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA