| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
WHI-P154 is a novel, potent and selective JAK3 (Janus kinase) inhibitor with potential antitumor activity. It shows no action against JAK1 or JAK2, and inhibits JAK3 with an IC50 of 1.8 μM. It also inhibits EGFR (IC50 = 4 nM), Src, Abl, VEGFR, and MAPK. Furthermore, it stops Stat3 phosphorylation but not Stat5 phosphorylation. Strong antiproliferative activity in vitro and strong antitumor efficaciousness in vivo are demonstrated by WHI-P154. Additionally, it prevents the in vitro production of NO, iNOS expression, and STAT1 activation in macrophages.
| Targets |
EGFR (IC50 = 4 nM); VEGFR (IC50 = 100 nM); Src (IC50 = 100 nM); JAK3 (IC50 = 1.8 μM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
WHI-P154 is tested in kinase assays. In order to provide a good approximation of specificity, the panel of kinases is chosen to cover the kinome broadly. Recombinant rat (IKKβ) or human (all other) full-length or GST-kinase domain fusion proteins are utilized for all kinases. AKT, AuroraA, cdk2, cdk6, CHK1, FGFR1, GSK3b, IKKb, IKKi, INSR, MAPK1, MAPKAP-K2, MASK, MET, PAK4, PDK1, PKCb, ROCK1, TaoK3, TrkA, and WHI-P154 are the kinases for which WHI-P154 is inactive (concentration that inhibits response by 50% [IC50] > 30 μM).
|
|
| Cell Assay |
A 96-well plate is seeded with 2.5×104 cells/well, and the cells are incubated at 37 °C for 36 hours prior to drug exposure. Fresh medium containing quinazoline compounds WHI-P154 at concentrations ranging from 0.1 μM to 250 μM is added to the wells on treatment day after the culture medium has been carefully aspirated out of them. For every treatment, three duplicate wells are utilized. The compound is added to the cells and incubated for 24 to 36 hours at 37 °C in a humidified 5% CO2 environment. After adding 10 μL of MTT (final concentration: 0.5 mg/mL) to each well, the plate is incubated for 4 hours at 37 °C. Then dissolved in a solution containing 10% SDS in 0.01 M HCL for an entire night at 37 °C. In a microplate reader, the absorbance of each well is measured at 570 nm.
|
|
| Animal Protocol |
SCID Xenograft Model of Human Glioblastoma (U737)
0.5 mg/kg or 1 mg/kg for 10 days i.p. |
|
| References |
| Molecular Formula |
C16H14BRN3O3
|
|
|---|---|---|
| Molecular Weight |
376.2
|
|
| Exact Mass |
375.021
|
|
| Elemental Analysis |
C, 51.08; H, 3.75; Br, 21.24; N, 11.17; O, 12.76
|
|
| CAS # |
211555-04-3
|
|
| Related CAS # |
|
|
| PubChem CID |
3795
|
|
| Appearance |
White to grey solid powder
|
|
| Density |
1.6±0.1 g/cm3
|
|
| Boiling Point |
470.3±45.0 °C at 760 mmHg
|
|
| Melting Point |
230 °C
|
|
| Flash Point |
238.2±28.7 °C
|
|
| Vapour Pressure |
0.0±1.2 mmHg at 25°C
|
|
| Index of Refraction |
1.703
|
|
| LogP |
4.15
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
23
|
|
| Complexity |
390
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
BrC1=C(C([H])=C([H])C(=C1[H])N([H])C1C2=C([H])C(=C(C([H])=C2N=C([H])N=1)OC([H])([H])[H])OC([H])([H])[H])O[H]
|
|
| InChi Key |
CBIAKDAYHRWZCU-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C16H14BrN3O3/c1-22-14-6-10-12(7-15(14)23-2)18-8-19-16(10)20-9-3-4-13(21)11(17)5-9/h3-8,21H,1-2H3,(H,18,19,20)
|
|
| Chemical Name |
2-bromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol
|
|
| Synonyms |
Janex1; WHIP-154; WHI P154; WHIP154
|
|
| 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 (6.65 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 (6.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6582 mL | 13.2908 mL | 26.5816 mL | |
| 5 mM | 0.5316 mL | 2.6582 mL | 5.3163 mL | |
| 10 mM | 0.2658 mL | 1.3291 mL | 2.6582 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.
Compounds, enzyme inhibition, and in vivo activity of kinase inhibitors studied. (A) Compound structures and molecular weights. (B) Heat map of kinase inhibition, IC50 (nM). (C) Efficacy of PF-956980 in murine delayed type hypersensitivity.Blood.2008 Feb 15;111(4):2155-7. |
Cytotoxicity of WHI-P154 in the drug-resistant and parental sensitive cells.Cancer Sci.2014 Aug;105(8):1071-8. |
Effect of WHI-P154 on the accumulation and efflux of [3H]-MX.Cancer Sci.2014 Aug;105(8):1071-8. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
