生物活性

• 靶点

  JAK2 IC50:2.30μM

  STAT3 IC50:2.43μM

• 描述The JAK/STAT3 pathway is activated by various cancer types, including glioma, and blockade of the pathway induces cell death in cancer cells. Thus, the JAK/STAT3 pathway is a target for cancer therapy. WP1066 induces degradation of JAK2 and inhibition of its phosphorylation. WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways^[3]. WP1066 is a most potent, small molecule, nonphosphorylated STAT3 inhibitor, that strongly binds to STAT3 protein with K_D of 300 nM. The IC₅₀ value in HEL cells is 2.3 μM^[4]. In a vitro study, AML (acute myelocytic leukemia) cells obtained from the four patients with AML were cultured using the AML blast colony culture assay with or without WP1066 at concentrations ranging from 0.5 to 3.0 μM. The result showed that WP1066 inhibited the proliferation of AML blast colony-forming cells in a dose-dependent manner^[5]. In a vivo study, mice with intracerebral melanoma were treated with WP1066 at a dose of 40 mg/kg for 21 days. The result showed that WP1066 could significantly increase the survival rate of intracerebral melanoma mice^[6]. Use WP1066 at different concentrations from 0 to10 µM on SNK6 cells to demonstrate the influence of WP1066 on protein expression of p-STAT3 and downstream molecules. The decrease of protein expression for p-STAT3 in SNK6 cells after a 24-h treatment of WP1066 in a dose-dependent manner which indicated the inhibition of the pro-survival factors downstream of STAT3 pathway may be the potential mechanisms contributing to the antitumor effect of WP1066 in nasal NKTCL(Nasal-type natural killer/T-cell lymphoma) cells^[7].
• 作用机制WP1066 can strongly bind to STAT3 protein and bind to the enzyme pocket of JAK2.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  human 30M cells	-	Cytotoxic assay	8 days	Cytotoxicity against human 30M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=1.8 μM	24900612
  human 73M cells	-	Cytotoxic assay	8 days	Cytotoxicity against human 73M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=2.1 μM	24900612
  human MM1 cells	-	Function assay	24-72 h	Antitumor activity against human MM1 cells after 24 to 72 hrs by MTT assay, ic50=1.2 μM	22036213

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01904123	Metastatic Malignant Neoplasm ... more >>in the Brain Metastatic Melanoma Recurrent Brain Neoplasm Recurrent Glioblastoma Recurrent Malignant Glioma Collapse <<	Phase 1	Recruiting	July 31, 2021	United States, Texas ... more >> M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Amy B. Heimberger    713-563-8717       Principal Investigator: Amy B. Heimberger Collapse <<