"目录号: HY-15312
EpigeneticsStem Cell/WntJAK/STAT Signaling-
WP1066 是一种新颖的JAK2和STAT3抑制剂，对 STAT5 和 ERK1/2 也起作用，但对 JAK1 和 JAK3 没有影响。
STATJAK
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生物活性
Description
WP1066 is a novel inhibitor ofJAK2andSTAT3, and also shows effect on STAT5 and ERK1/2, without affecting JAK1 and JAK3.
IC50& Target
IC50: 2.3 μM (JAK2), 2.43 μM (STAT3)
In Vitro
WP1066 markedly inhibits the growth of HEL cells in a dose-dependent manner. The IC50value for inhibition of the proliferation of HEL cells is 2.3 μM. WP1066 inhibits the growth of human HEL cells carrying the JAK2 V617F mutant isoform[1]. Blockade of p-STAT3 with WP1066 enhances the cytotoxic effects of CTX on the tumor. The IC50doses of WP1066 for B16 cells is 2.43 μM (0.865 μg/mL)[2]. WP1066 inhibits AML blast colony-forming cell proliferation, suppresses normal BM progenitor proliferation at increased concentrations, and inhibits AML colony-forming cell proliferation[3].
In Vivo
WP1066 (30 mg/kg, o.g.)does not further enhance the therapeutic effects of cyclophosphamide on pulmonary melanoma lesions, enhance the therapeutic effects of cyclophosphamide against CNS melanoma, or further enhance immune-mediated cytotoxic effects of CTX in C57BL/6J mice. WP1066 exerts an additive effect to CTX inhibition of the p-STAT3 pathway within the tumor microenvironment[2].
Clinical Trial
NCT01904123
M.D. Anderson Cancer Center-National Institutes of Health (NIH)-National Cancer Institute (NCI)
Brain Cancer-Central Nervous System Neoplasms-Melanoma-Solid Tumors
September 2017
Phase 1
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References
[1].Verstovsek S, et al. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res, 2008, (3), 788-796.
[2].Hatiboglu MA, et al. The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models. Int J Cancer, 2012, 131(1), 8-17
[3].Ferrajoli A, et al. WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res, 2007, 67(23), 11291-11299.