WHI-P154

Catalog No.S2867 Batch:S286701

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Technical Data

Formula

C16H14BrN3O3
Molecular Weight 376.2 CAS No. 211555-04-3
Solubility (25°C)* In vitro DMSO 75 mg/mL (199.36 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%propylene glycol 5%Tween80 65%D5W
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM, no activity against JAK1 or JAK2, also inhibits EGFR, Src, Abl, VEGFR and MAPK, prevents Stat3, but not Stat5 phosphorylation.
Targets
EGFR [1] VEGFR [1] Src [1] JAK3 [1]
4 nM 100 nM 100 nM 1.8 μM
In vitro WHI-P154 is first described as a JAK3 inhibitor that displays no activity at JAK1 or JAK2. WHI-P154 inhibits STAT1 activation, iNOS expression and NO production in macrophages in vitro. But it is proved that WHI-P154 also inhibits other common kinases including EGFR, Src, Abl, VEGFR, MAPK and PI3-K and induces apoptosis in human glioblastoma cell lines. [1] WHI-P154 inhibits glioblastoma cell adhesion and migration in the context of ECM.[2] WHI-P154 exhibits significant cytotoxicity against U373 and U87 human glioblastoma cell lines, causing apoptotic cell death at micromolar concentrations. The in vitro antiglioblastoma activity of WHI-P154 is amplified > 200-fold and rendered selective by conjugation to recombinant human epidermal growth factor (EGF). In vitro treatment with EGF-P154 results killing of glioblastoma cells at nanomolar concentrations with an IC50 of 813 nM, whereas no cytotoxicity against EGF-R-negative leukemia cellsis observed, even at concentrations as high as 100 mM.[3]
In vivo The in vivo administration of EGF-P154 results in delayed tumor progression and improved tumor-free survival in a severe combined immunodeficient mouse glioblastoma xenograft model. Whereas none of the control mice remain alive tumor-free beyond 33 days (median tumor-free survival, 19 days) and all control mice have tumors that rapidly progress to reach an average size of > 500 mm3 by 58 days, 40% of mice treated for 10 consecutive days with 1 mg/kg/day EGF-P154 remain alive and free of detectable tumors for more than 58 days with a median tumor-free survival of 40 days. The tumors developing in the remaining 60% of the mice never reache a size > 50 mm3.[3]

Protocol (from reference)

Kinase Assay:[1]
  • Kinase assays

    WHI-P154 is tested in kinase assays. The panel of kinases is selected to broadly cover the kinome, providing a good approximation of specificity. For all kinases, recombinant rat (IKKβ) or human (all others), full-length or GST-kinase domain fusion proteins, are used. WHI-P154 is inactive (concentration that inhibits response by 50% [IC50] > 30 μM) for the following kinases: AKT, AuroraA, cdk2, cdk6, CHK1, FGFR1, GSK3b, IKKb, IKKi, INSR, MAPK1, MAPKAP-K2, MASK, MET, PAK4, PDK1, PKCb, ROCK1, TaoK3, TrkA.
Cell Assay:[3]
  • Cell lines

    U87, U737

  • Concentrations

    0.1-250 μM

  • Incubation Time

    24-36 h

  • Method

    Cells are seeded into a 96-well plate at a density of 2.5×104 cells/well and incubated for 36 h at 37 ℃ before drug exposure. On the day of treatment, culture medium is carefully aspirated from the wells and replaced with fresh medium containing the quinazoline compounds WHI-P154 at concentrations ranging from 0.1 μM to 250 μM. Triplicate wells are used for each treatment. The cells are incubated with the compound for 24hours to 36hours at 37 ℃ in a humidified 5% CO2 atmosphere. To each well, 10 μL of MTT (final concentration, 0.5 mg/mL) is added, and the plate are incubated at 37 ℃ for 4 h. Than solubilized overnight at 37 ℃ in a solution containing 10% SDS in 0.01 M HCL. The absorbance of each well is measured in a microplate reader at 570 nm.
Animal Study:[3]
  • Animal Models

    SCID Xenograft Model of Human Glioblastoma (U737)

  • Dosages

    0.5 mg/kg or 1 mg/kg for 10 days

  • Administration

    i.p.

Customer Product Validation

,

Data from [Data independently produced by , , J Mol Med, 2018, doi:10.1007/s00109-018-1724-8]

Data from [Data independently produced by , , Biol Open, 2018, 7(1)]

Selleck's WHI-P154 has been cited by 13 publications

Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis [ Nat Commun, 2023, 14(1):6908] PubMed: 37903763
Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis [ Nat Commun, 2023, 14(1):6908] PubMed: 37903763
Tyrosine Kinase Inhibitor Profiling Using Multiple Forskolin-Responsive Reporter Cells [ Int J Mol Sci, 2023, 10.3390/ijms241813863] PubMed: 37762164
Tyrosine Kinase Inhibitor Profiling Using Multiple Forskolin-Responsive Reporter Cells [ Int J Mol Sci, 2023, 24(18)13863] PubMed: 37762164
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Interleukin 6 trans-signaling is a critical driver of lung allograft fibrosis [ Am J Transplant, 2021, 21(7):2360-2371] PubMed: 33249747
Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model [ J Med Chem, 2020, 31] PubMed: 32191458
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
IL-21 promotes osteoblastic differentiation of human valvular interstitial cells through the JAK3/STAT3 pathway [ Int J Med Sci, 2020, 17(18):3065-3072] PubMed: 33173427
Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway [Zhou Y, et al. J Mol Med, 2018, 10.1007/s00109-018-1724-8] PubMed: 30483821

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.