WHI-P154

Alias: Janex1; WHIP-154; WHI P154; WHIP154
Cat No.:V0340 Purity: ≥98%
WHI-P154 is a novel, potent and selective JAK3 (Janus kinase) inhibitor with potential antitumor activity.
WHI-P154 Chemical Structure CAS No.: 211555-04-3
Product category: EGFR
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
Targets
EGFR (IC50 = 4 nM); VEGFR (IC50 = 100 nM); Src (IC50 = 100 nM); JAK3 (IC50 = 1.8 μM)
ln Vitro

WHI-P154 is first described as a JAK3 inhibitor that displays no activity at JAK1 or JAK2. In vitro, WHI-P154 prevents macrophages from producing NO, iNOS expression, and STAT1 activation. WHI-P154, however, has been shown to also cause apoptosis in human glioblastoma cell lines and to inhibit other common kinases such as EGFR, Src, Abl, VEGFR, MAPK, and PI3-K.[1] In an ECM environment, WHI-P154 prevents glioblastoma cells from adhering to surfaces and migrating.[2] WHI-P154 causes apoptotic cell death at micromolar concentrations and demonstrates significant cytotoxicity against human glioblastoma cell lines, U373 and U87. By conjugating to recombinant human epidermal growth factor (EGF), WHI-P154'sinvitro antiglioblastoma activity is amplified more than 200 times and obtained selectivity. While EGF-R-negative leukemia cells show no cytotoxicity against EGF-P154 in vitro treatment, even at concentrations as high as 100 mM, glioblastoma cells are killed by the protein at nanomolar concentrations with an IC50 of 813 nM.[3]

ln Vivo
In a severe combined immunodeficient mouse glioblastoma xenograft model, the in vivo administration of EGF-P154 results in delayed tumor progression and improved tumor-free survival. Although the tumors in all control mice grow quickly and reach an average size of more than 500 mm3 by 58 days, 40% of mice treated for 10 consecutive days with 1 mg/kg/day survived without a tumor after 33 days (median tumor-free survival, 19 days). EGF-P154 have a median tumor-free survival of 40 days and can live for more than 58 days without any discernible tumors. In the remaining 60% of mice, the tumors never grow to a size larger than 50 mm3.[3]
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

[1]. Blood . 2008 Feb 15;111(4):2155-7.

[2]. Clin Cancer Res . 1998 Oct;4(10):2463-71.

[3]. Clin Cancer Res . 1998 Jun;4(6):1405-14.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C16H14BRN3O3
Molecular Weight
376.2
Exact Mass
375.02
Elemental Analysis
C, 51.08; H, 3.75; Br, 21.24; N, 11.17; O, 12.76
CAS #
211555-04-3
Appearance
White to grey solid powder
SMILES
COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)O)Br)OC
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 Data
Solubility (In Vitro)
DMSO: ~71 mg/mL (~199.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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Biological Data
  • WHI-P154

    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.

  • WHI-P154

    Cytotoxicity of WHI-P154 in the drug-resistant and parental sensitive cells.2014 Aug;105(8):1071-8.

  • WHI-P154

    Effect of WHI-P154 on the accumulation and efflux of [3H]-MX.2014 Aug;105(8):1071-8.

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