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 Oct 2026·PROTEIN AND PEPTIDE LETTERS

Aloperine Protects Against Cisplatin-Induced Injury in Kidney Cells Via Modulating PI3K/AKT/Nfκb-Mediated NLRP3 Inflammasome

Article

Author: Wang, Xuguang ; Zhang, Shuai ; Liu, Jie ; Liang, Jinglan ; Qiu, Mingning

Background::

Aloperine (ALO) is a vital alkaloid present in the traditional Chinese herb Sophora alopecuroides, which has demonstrated effective anti-inflammatory activity. However, the effects and the mechanism of action of ALO on cisplatin (CDDP)-induced nephrotoxicity remain unclear.

Objective::

This study aimed to investigate the effects of ALO on CDDP-induced nephrotoxicity and its potential mechanism of action in vitro.

Methods::

Cell viability, lactate dehydrogenase cytotoxicity, apoptosis, activity of Caspase-Glo 3/7 and 1, in-cell western blotting, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA) were performed to assess the influence of ALO on CDDP-treated kidney cells. Inhibitors of phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, AKT inhibitor VIII), and nuclear factor kappa B (NFκB, BAY 11-7082) were used to determine their potential mechanisms of action.

Results::

The results indicated that ALO significantly reversed the inhibition of cell viability, cytotoxicity, apoptosis, and the release of inflammatory factors induced by CDDP in kidney cells. ALO attenuated the PI3K/AKT/NFκB-mediated pathway activated by CDDP treatment and downregulated the CDDP-induced nucleotide-binding domain, leucine-rich-containing family, pyrin domain–containing-3 (NLRP3) inflammasome. Furthermore, the PI3K and AKT inhibitors diminished the effects of ALO on CDDP-treated kidney cells. Additionally, NFκB inhibitors reversed the effects of the PI3K and AKT inhibitors on ALO in CDDP-treated kidney cells.

Conclusion::

These results suggest that ALO protects against CDDP-induced injury in kidney cells by modulating the PI3K/AKT/NFκB-mediated NLRP3 inflammasome.

01 Jun 2026·CELLULAR SIGNALLING

Glycoprotein non-metastatic melanoma protein B promotes pyroptosis of macrophages induced by homocysteine associated with the upregulation of the NOX-2/ NF-κB signaling pathway

Article

Author: Ding, Xueqin ; Zhang, Xuhong ; Yang, Xiaoming ; Cao, Ping ; Liu, Yinjuan ; Ma, Xiaohong ; Tian, Tian

Elevated homocysteine (Hcy) levels are well established as an independent risk factor for atherosclerosis and its associated cardiovascular diseases. Macrophage pyroptosis- mediated inflammation plays a crucial role in the progression of atherosclerosis. Notably, glycoprotein non-metastatic melanoma protein B (GPNMB) expression is increased in macrophages within atherosclerotic plaques; however, whether GPNMB participates in Hcy-induced macrophage pyroptosis remains elusive. In the present study, we found that GPNMB expression was upregulated in Hcy- treated THP-1- derived macrophages. Consistently, serum GPNMB levels were significantly higher in patients with hyperhomocysteinemia (HHcy) compared with healthy controls. Functional experiments showed that silencing GPNMB reduced Hcy-triggered pyroptosis in THP-1-derived macrophages, whereas GPNMB overexpression exerted the opposite effect. Mechanistically, GPNMB upregulated the NOX2/NF-κB signaling pathway in THP-1-derived macrophages. Importantly, the pro-pyroptotic effect of GPNMB overexpression in Hcy-treated THP-1-derived macrophages was counteracted by either inhibition of NADPH oxidase 2 (NOX2) using the specific inhibitor gp91ds-tat or blockade of NF-κB activation with the inhibitor BAY11-7082. Moreover, serum GPNMB levels were correlated with serum Hcy levels and lipid profiles in both healthy individuals and HHcy patients. Collectively, these findings demonstrate that GPNMB facilitates Hcy-induced macrophage pyroptosis associated with the upregulation of the NOX2/NF-κB signaling pathway, highlighting the potential relevance of GPNMB as a candidate target for the clinical management of HHcy-related atherosclerotic cardiovascular disease.

100 Deals associated with BAY-11-7083

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