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 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MPAEpiC cells
150, 300, 600 nM
6 h
To evaluate the inhibitory effect of TPCA-1 on LPS-induced inflammatory response, results showed that TPCA-1 significantly suppressed the expression of IL-1B, IL-6, IL-8, IL-15, TNFA, MIP2, CCR5, GM-CSF, VEGF, COX2, and iNOS.
Biol Direct. 2024 Jun 21;19(1):48.
RAW264.7 cells
150, 300, 600 nM
6 h
To evaluate the inhibitory effect of TPCA-1 on LPS-induced inflammatory response, results showed that TPCA-1 significantly suppressed the expression of IL-1B, IL-6, IL-8, IL-15, TNFA, MIP2, CCR5, GM-CSF, VEGF, COX2, and iNOS.
Biol Direct. 2024 Jun 21;19(1):48.
mammary epithelial cells
25 μM
24 h
To test the effect of TPCA-1 on Bcl11b expression, it was found that TPCA-1 significantly upregulated Bcl11b expression
Nat Commun. 2024 Jun 17;15(1):5154.
human umbilical vein endothelial cells (HUVECs)
3 μM
1 h
TPCA-1 inhibits NF-κB signaling, reducing the expression of lncRNA-CCL2 and CCL2
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16410-16419.
BMDCs
10 µM
1 h
Inhibition of IKK-2-dependent phosphorylation of SNAP23, blocking MHC-I delivery to phagosomes, but TPCA-1 had no effect on MHC-I delivery and cross-presentation in Tap−/− DCs.
Nat Immunol. 2021 Apr;22(4):497-509.
BUMPT cells
50 μM
24 h
TPCA1 significantly reduced the levels of P65 phosphorylation and cleavage of caspase 3 in BUMPT cells treated with cisplatin and sTim-3.
Cell Death Discov. 2023 Jul 1;9(1):218.
TPCA-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Palb2 mutant mice
Intraperitoneal injection
20 mg/kg
Twice, 12 hours apart
Inhibit NFκB, restore radiation-induced apoptosis, and delay tumor development
Cancer Res. 2018 Jul 15;78(14):3969-3981
Nude mice
SW620 and HCT116 xenograft models
Intraperitoneal injection
15 mg/kg
Once every two days, until the end of the experiment
The combination of TPCA-1 with trametinib significantly inhibited the growth of PPP6C-deficient tumors and restored their sensitivity to MAPK pathway inhibitors.
Sci Signal. 2024 May 14;17(836):eadd5073
C57BL/6 mice
ARDS mouse model
Not specified
10 mg/kg
Once daily for two days
To evaluate the inhibitory effect of TPCA-1 on inflammatory response in ARDS mice, results showed that TPCA-1 significantly reduced serum concentrations of IL-1β, IL-6, and TNF-α, but did not affect concentrations of IL-15, IL-18, and IFN-γ.
Biol Direct. 2024 Jun 21;19(1):48.
Mice
Aged mice
Intraperitoneal injection
10 mg/kg
Once daily for 30 days
To test the effect of TPCA-1 on mammary cell aging, it was found that TPCA-1 significantly reduced the number of senescent cells and increased the number of young cells
Nat Commun. 2024 Jun 17;15(1):5154.
CD-1 mice
Acute lung inflammation mouse model
Intravenous injection
2 mg/kg
Single dose, lasting 20 hours
To evaluate the therapeutic effect of TPCA-1-NPs-Abs in the acute lung inflammation mouse model, results showed that anti-ICAM-1 decorated NPs significantly reduced lung inflammation.
ACS Appl Mater Interfaces. 2019 May 8;11(18):16380-16390
Mice
Cisplatin-induced acute kidney injury model
Tail vein injection
1 mg/kg
Single injection, lasting 3 days
TPCA1 significantly reduced serum creatinine and BUN levels in cisplatin-treated Tim-3 knockout mice and alleviated renal tubular injury.
Cell Death Discov. 2023 Jul 1;9(1):218.
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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