Home JAK/STAT JAK inhibitor - EGFR inhibitor WHI-P154

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WHI-P154 JAK inhibitor

Cat.No.S2867

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.
WHI-P154 JAK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 376.2

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Quality Control

Batch: S286701 DMSO]75 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.77%
99.77

Chemical Information, Storage & Stability

Molecular Weight 376.2 Formula

C16H14BrN3O3

 Storage (From the date of receipt)
CAS No. 211555-04-3 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)O)Br)OC

Solubility

In vitro
Batch:

DMSO : 75 mg/mL (199.36 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
EGFR [1]
4 nM
VEGFR [1]
100 nM
Src [1]
100 nM
JAK3 [1]
1.8 μM
In vitro
WHI-P154 is first described as a JAK3 inhibitor that displays no activity at JAK1 or JAK2. This compound inhibits STAT1 activation, iNOS expression and NO production in macrophages in vitro. But it is proved that this chemical also inhibits other common kinases including EGFR, Src, Abl, VEGFR, MAPK and PI3-K and induces apoptosis in human glioblastoma cell lines. [1] It inhibits glioblastoma cell adhesion and migration in the context of ECM.[2] This compound exhibits significant cytotoxicity against U373 and U87 human glioblastoma cell lines, causing apoptotic cell death at micromolar concentrations. The in vitro antiglioblastoma activity of this chemical 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]
Kinase Assay
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. This compound 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.
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 this compound 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]
References

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