WHI-P154 (C09-1084-508)

InformationWHI-P154 is a potentJAK3inhibitor withIC50of 1.8 μM, no activity against JAK1 or JAK2, also inhibits EGFR, Src, Abl, VEGFR and MAPK, prevents Stat3, but not Stat5 phosphorylation.In vitroWHI-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. WHI-P154 inhibits glioblastoma cell adhesion and migration in the context of ECM. 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.In vivoThe 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.Cell Datacell lines：Concentrations：0.1-250 μMIncubation Time：24-36 hPowder Purity:≥99%. Specifications and Purity: 10mM in DMSO. Molecular Formula: C16H14BrN3O3. Molecular Weight: 376.2.