Delving into the Latest Updates on NF-κB inhibitor(TianJin Hospital) with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms

1,3,5-triazine derivatives

Target

NF-κB x TLR4

Action

inhibitors, antagonists

Mechanism

NF-κB inhibitors(Nuclear factor NF-kappa-B complex inhibitors), TLR4 antagonists(Toll like receptor 4 antagonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Spinal Cord Injuries

Inactive Indication-

Originator Organization

Tianjin Hospital

Active Organization

Tianjin Hospital

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

This study examined the effects of TMAO (100–400 μmol/L) on oocyte maturation, cumulus cell expansion, mitochondrial distribution, and embryonic development in vitro and in a BALB/c mouse model. The involvement of the NF-κB/NLRP3 signaling pathway in TMAO-induced ovarian dysfunction was assessed using Western blotting and gene expression analyses. The potential therapeutic effect of miRNA-146, an NF-κB inhibitor, was also explored.

Results::

Western blotting confirmed that TMAO activates the NF-κB signaling pathway and induces the synthesis of caspase 3 and NLRP3 complexes. However, pretreatment with miRNA-146, an NF-κB inhibitor, significantly reduced inflammation and inflammatory gene expression during TMAO therapy. Additionally, miRNA-146 pretreatment promoted oocyte maturation by suppressing NF-κB/NLRP3 activation, OGCs apoptotic inflammatory factor expression, and the gene expression of NF-κB, caspase 3, and NLRP3.

Conclusion::

Findings demonstrate that TMAO disrupts oocyte development through NF- κB/NLRP3 activation, contributing to ovarian dysfunction. Notably, targeting TMAO and its downstream signaling could serve as a novel therapeutic strategy for premature ovarian insufficiency (POI).

01 Dec 2025·NEUROPHARMACOLOGY

P2X7R-NF-κB-PDI signal pathway regulates LPS-induced impaired GSH synthesis by modulating ATF4-mediated xCT upregulation, S-nitrosylation of ASCT2 and GSHS expressions in the mouse hippocampus

Article

Author: Wang, Su Hyeon ; Kim, Ji-Eun ; Lee, Duk-Shin

Protein disulfide isomerase (PDI) augments lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation by integrating Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) signaling pathways in a positive feedback manner. However, it has been largely unknown whether PDI is involved in altered glutathione (GSH) biosynthesis, which is mediated by P2X7R, in response to LPS. In the present study, LPS-induced NF-κB activation increased PDI expression, but decreased solute carrier 1 A5 (ASCT2) level in the P2X7^+/+ mouse hippocampus. PDI knockdown attenuated ASCT2 downregulation and S-nitrosylated (SNO-) ASCT2 level in response to LPS. This LPS-induced NF-κB-PDI activation also increased activating transcription factor 4 (ATF4) expression in astrocytes, which elicited cystine:glutamate transporter (xCT) upregulation, but decreased ASCT2 and GSH synthetase (GSHS) expression. Furthermore, S-nitrosylation of PDI modulated ATF4-mediated xCT upregulation in response to LPS. SN50 (a NF-κB inhibitor), PDI knockdown and ATF4 siRNA mitigated the decreased GSH content induced by LPS. Under physiological condition, P2X7R deletion did not affect basal PDI, ATF4, xCT and SNO-ASCT2 levels. However, it increased ASCT2 expression and decreased SNO-PDI level. P2X7R ablation ameliorated (1) PDI, ATF4 and xCT2 upregulations, (2) S-nitrosylation of ASCT2 and PDI and (3) ASCT2 downregulation in response to LPS. These findings indicate that P2X7R-NF-κB-PDI signal pathway may inhibit GSH biosynthesis in response to LPS by modulating expression/S-nitrosylation of ASCT2 and ATF4-mediated xCT regulation in response to LPS.

01 Dec 2025·MOLECULAR BIOLOGY REPORTS

Differential effects of minocycline on human breast epithelial cells, human breast cancer cells and their tumor hybrids

Article

Author: Weiler, Julian ; Moayed, Fuad ; Dittmar, Thomas ; Keil, Silvia

Abstract:

Background:

The antibiotic minocycline has been suggested as a potential agent in cancer therapy due to its anti-inflammatory properties and effectiveness as an NF-κB inhibitor. In previous studies, we showed that minocycline could effectively block the fusion of breast epithelial cells and cancer cells. However, its influence on breast cancer cell characteristics, including proliferation, migration, and gene expression has not yet been investigated.

Methods:

M13SV1-EGFP-Neo breast epithelial cells, HS578T-Hyg breast cancer cells and M13HS-2 and M13HS-8 tumor hybrids were used as breast (cancer) model cell lines in this study. Cells were treated with up to 50 µg/ml minocycline. An XTT assay and a colony formation assay were used to study cell proliferation. Western blot analysis and Zymography were used to examine the expression of MMP-2 and MMP-9, EMT, and stemness marker. Cell migration was measured by Scratch assay. Using a two-way ANOVA and the Tukey post-hoc test, statistical significance was determined.

Results:

Minocycline inhibited proliferation and colony formation capacity in a dose-dependent manner, whereas EMT and stemness marker expression remained unchanged in all cell lines. Zymography data showed that MMP-2 and MMP-9 expression was down-regulated M13SV1-EGFP-Neo treated with minocycline, but not in HS578T-Hyg cells or M13HS-2 and M13HS-8 tumor hybrids. Minocycline inhibited the migration of M13SV1-EGFP-Neo cells in a dose-dependent manner, while the migration of HS578T-Hyg, M13HS-2 and M13HS-8 tumor hybrid cells necessitated a minimum of 25 µg/ml minocycline,

Conclusions:

The results showed that non-malignant cells and neoplastic cells reacted differently to minocycline. This could mean that minocycline will have unwanted side effects if it is used in cancer therapy.

100 Deals associated with NF-κB inhibitor(TianJin Hospital)

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