- 貨號 Cat. No.
- S2867
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
WHI-P154
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.
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10mM/1mLIn DMSO |
USD 176 |
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10mg |
USD 138 |
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50mg |
USD 592 |
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
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. |
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Targets |
JAK3 |
EGFR |
VEGFR |
Src |
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IC50 |
1.8 μM |
4 nM |
100 nM |
100 nM [1] |
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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] |
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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] |
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Features |
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Protocol(Only for 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. |
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Cell Assay: [3]
Cell lines |
U87, U737 |
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Concentrations |
0.1-250 μM |
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Incubation Time |
24-36 h |
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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. |
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Animal Study: [3]
Animal Models |
SCID Xenograft Model of Human Glioblastoma (U737) |
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Dosages |
0.5 mg/kg or 1 mg/kg for 10 days |
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Administration |
i.p. |
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Solubility |
30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL |
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1
References
Download WHI-P154 SDF
Molecular Weight (MW) |
376.2 |
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Formula |
C16H14BrN3O3
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CAS No. |
211555-04-3 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
75 mg/mL (199 mM) |
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Water |
<1 mg/mL (<1 mM) |
Ethanol |
<1 mg/mL (<1 mM) |
In vivo |
30% propylene glycol, 5% Tween 80, 65% D5W, |
30 mg/mL |
* <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. |
Chemical Name |
Phenol, 2-bromo-4-[(6,7-dimethoxy-4-quinazolinyl)amino]- |
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Stock Solution (1ml DMSO) |
1mM |
10mM |
20mM |
30mM |
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Mass(mg) |
0.3762 |
3.762 |
7.524 |
11.286 |
Customer Reviews (1)
Click to enlarge |
Rating |
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Source |
WHI-P154 purchased from Selleck |
Method |
MTT Assay |
Cell Lines |
NCI-H460/MX20 cells |
Concentrations |
4 μM |
Incubation Time |
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Results |
Reversal effect of WHI-P154 on the sensitivity of NCI-H460/MX20 cells to mitoxantrone. |
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