TPCA-1 effectively suppresses the production of TNF-α, IL-6, and IL-8 in human monocytes triggered by lipopolysaccharide, with an IC50 ranging from 170 to 320 nM[1][2]. TPCA-1, at concentrations ranging from 0 to 2 μM, dose-dependently and over time, impedes the phosphorylation and transactivation of STAT3 caused by cytokines and nonreceptor tyrosine kinases. It fully halts the phosphorylation of STAT3 while maintaining the overall levels of STAT3 unchanged[3] TPCA-1 enhances the responsiveness to ZD1839 across cell lines that are either sensitive or resistant to tyrosine kinase inhibitors. In human peripheral blood monocytes activated with LPS, TPCA-1, at concentrations from 0 to 10 μM over approximately 24 hours, curtails the production of TNF-α, IL-6, and IL-8. This inhibition of LPS-induced cytokine production confirms the compound's effectiveness in cell viability assays. In cancer cell lines HCC827 and H1975, TPCA-1, administered in the same concentration range for 0.5 to 2 hours, inhibits cell proliferation and induces a G2-M phase cell-cycle arrest in HCC827 cells, but not in A549 cells[3].
TPCA-1 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
C57BL/6 mouse BMDM cells
Cytotoxicity assay
24 h
Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs
22533790
C57BL/6 mouse BMDM cells
0.5 μM
Function assay
1 h
Antiinflammatory activity in C57BL/6 mouse BMDM cells assessed as inhibition of LPS-stimulated TNFalpha production at 0.5 uM pretreated for 1 hr before LPS challenge after 8 to 24 hrs by immunoassay
22533790
TPCA-1 动物研究
Animal study
TPCA-1, administered at dosages of 3, 10, or 20 mg/kg intraperitoneally, leads to a dose-dependent mitigation of murine collagen-induced arthritis (CIA) severity[2]. Additionally, a daily intraperitoneal injection of TPCA-1 at 10 mg/kg enhances the therapeutic effects of ZD1839 in xenograft models, particularly inhibiting the growth of non-small cell lung cancer (NSCLC) with EGFR mutations. The treatment, given twice daily from days 1 to 47, not only lessens the severity but also delays the onset of CIA and reduces antigen-induced T cell proliferation ex vivo, tested using a six-week-old BALB/c female nude mice model, which was subcutaneously injected with HCC827 cells (5×106[3].
Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs
22533790
C57BL/6 mouse BMDM cells
0.5 μM
Function assay
1 h
Antiinflammatory activity in C57BL/6 mouse BMDM cells assessed as inhibition of LPS-stimulated TNFalpha production at 0.5 uM pretreated for 1 hr before LPS challenge after 8 to 24 hrs by immunoassay
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