Delving into the Latest Updates on BAY-11-7083 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BAY-11-7082, BAY-11-7085, BAY-11-7821

+ [1]

Target

TNF-α

Action

inhibitors

Mechanism

TNF-α inhibitors(Tumor necrosis factor α inhibitors)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Inflammation

Originator Organization

Bayer Corp.

Active Organization-

Inactive Organization

Bayer Corp.

License Organization-

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Interleukin 1 beta (IL-1β) is upregulated following a tendon injury and in vitro studies have shown that it leads to numerous negative effects on tendon cell function and gene expression. IL-1β activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and we hypothesised that inhibiting NF-κB activation would mediate the negative effects of IL-1β on equine tendon cells in 3-dimensional (3D) cultures.

Methods and results:

Here, we tested three inhibitors of NF-κB signalling (Bortezomib, BAY11-7082 and Wedelolactone) along withTJ-M2010-5, an inhibitor of MyD88, which is a critical adaptor protein for mediating IL-1β signalling. None of these inhibitors were able to rescue gel contraction by equine tenocytes exposed to IL-1β in 3D culture. However, the daily application of the interleukin-1 receptor-associated kinase (IRAK)−4 inhibitor PF-06650833 resulted in a partial rescue of collagen contraction and interleukin-6 (IL-6) production by equine tenocytes in 3D culture. Global gene expression using RNA sequencing also revealed a partial rescue, although this was not as complete as that achieved using interleukin-1 receptor antagonist protein (IL1Ra), with many inflammatory pathways remaining upregulated. ENPP2 expression was significantly increased by IL-1β and rescued by both IL1Ra and PF-06650833 suggesting ENPP2 may be involved in collagen contraction. However, direct ENPP2 inhibition does not rescue IL-1β mediated inhibition of contraction and ENPP2 inhibition alone reduces collagen contraction.

Conclusions:

Together, this data demonstrates that IL-1β has a broad mechanism of action on tendon cells which cannot be fully mediated by targeting specific parts of the signalling pathway.

01 Feb 2026·ARCHIVES OF ORAL BIOLOGY

Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition

Article

Author: Shan, Chao ; Xia, Yuning ; Wu, Zeyu ; Zhao, Jin

OBJECTIVE:

This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenvironment.

DESIGN:

Network pharmacology and molecular docking were used to identify mulberry leaves' active constituents and their targets in periodontitis treatment. An inflammatory model was established in JBMMSCs using Porphyromonas gingivalis-lipopolysaccharide (5 μg/mL). TML's optimal concentration was determined via CCK-8 and ELISA. Osteogenic differentiation, inflammatory markers, and NF-κB pathway activity were assessed using ALP/ARS staining, RT-PCR, and Western blot (WB). A rat model of ligature-induced periodontitis was established, and TML's effects were evaluated through histopathological staining, micro-CT, RT-PCR, and WB. JBMMSCs from each animal experimental group were isolated for in vitro osteogenic validation. Mechanisms were clarified by comparing TML with the NF-κB inhibitor BAY11-7082.

RESULTS:

TML was identified as the key constituent targeting NF-κB and inflammatory mediators (IL-6, IL-1β, TNF-α). 5 μM TML significantly suppressed inflammatory cytokines, promoted osteogenic differentiation, and inhibited NF-κB activation in JBMMSCs. In rats, 30 mg/kg TML markedly reduced inflammation and alveolar bone loss, showing efficacy comparable to indomethacin, and JBMMSCs from TML-treated groups exhibited enhanced osteogenesis. TML's inhibition of NF-κB was similar to BAY11-7082.

CONCLUSION:

TML reduces periodontal inflammation and enhances the osteogenic potential of JBMMSCs by inhibiting the NF-κB pathway, providing a novel strategy for periodontitis-related bone regeneration.

01 Jan 2026·EXPERIMENTAL CELL RESEARCH

The RPE-derived NF-κB/HO-1/MCP-1 pathway mediated microglia recruitment involved in the outer blood-retinal barrier breakdown in experimental diabetic retinopathy

Article

Author: Shu, Yiyang ; Zhang, Jingfa ; Zhang, Chaoyang ; Liu, Dandan ; Bi, Yanlong ; Xie, Hai

PURPOSE:

To investigate the mechanisms underlying the microglia recruitment and its causal role in the breakdown of the outer blood-retinal barrier (oBRB) in diabetic retinopathy (DR).

METHODS:

The Sprague-Dawley rats were adopted to establish diabetic model by intraperitoneal injection of streptozotocin. Twelve weeks later, the retinal pigment epithelium (RPE)-choroid complexes and retinal paraffin sections were examined with immunofluorescence. RNA-sequencing was performed on glyoxal-treated ARPE-19 cells, followed by bioinformatic analysis to identify significant genes and pathways. Transwell assays were employed to establish the co-culture system and investigate the interactions between ARPE-19 and BV2 microglial cells. The results were further validated by the inhibitor or siRNAs targeting NF-κB, HO-1, and MCP-1.

RESULTS:

In 12-week diabetic rat retinas, microglia were observed to accumulate in the vicinity of the RPE cells, accompanied by the disruption of ZO-1. The expressions of ZO-1 and occludin remained largely unchanged in ARPE-19 cells when treated with glyoxal alone. However, when co-cultured with BV2 microglial cells, the expression levels of ZO-1 and occludin in glyoxal-treated ARPE-19 cells were significantly decreased, which were effectively prevented by siMCP-1. Mechanistically, RNA-sequencing analysis revealed that the activation of the NF-κB/HO-1/MCP-1 pathway in glyoxal-treated ARPE-19 cells significantly contributed to the recruitment of microglia. The above effects were reversed by BAY 11-7082, siHO-1 or siMCP-1.

CONCLUSION:

Under diabetic conditions, microglia are recruited by RPE cells via the NF-κB/HO-1/MCP-1 pathway, which subsequently results in the oBRB breakdown. This study provides a novel mechanistic insight for the interaction between microglia and RPE cells, and implies a potential therapeutic strategy for the treatment of DR.

100 Deals associated with BAY-11-7083

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