CRNDE alleviated IL-1β-induced injuries in OA chondrocytes by suppressing the miR-31-mediated NF-κB signaling pathway.

P2, N=24, Completed, Zydus Lifesciences Limited | Recruiting --> Completed | Trial primary completion date: Aug 2024 --> Nov 2024

BAY11-7082, which is an inhibitor of the inhibitor of nuclear factor κB protein α(IκBα), was used to explore the effect of the expression of phosphorylated nuclear factor κB(p-NF-κB) in the nucleus after the Fur treatment on the NOX4 protein level...In the stably transfected cell strain with PRDX1 gene knockout, the apoptosis rate is considerably higher than that of the negative control group after Fur treatment. The above results indicate that Fur can induce the apoptosis of colorectal cancer cells by promoting the signal transduction of NF-κB in the nucleus and increasing the generation of mitochondrial ROS derived from NOX4 to inhibit the PRDX1 protein expression.

P2, N=24, Completed, Zydus Lifesciences Limited | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Jun 2024

P2, N=96, Recruiting, NEXTGEN Bioscience | Not yet recruiting --> Recruiting | Phase classification: P2a --> P2

P1, N=67, Completed, NodThera Limited | Phase classification: P1/2 --> P1

We also observed that Allicin pretreatment reduced the NLRP3-related protein, such as Caspase-1 (P < 0.001) and increased the protein expressions of the PI3K/Akt pathway molecules, such as PI3K and Akt (all, P < 0.001). Our research data demonstrated that Allicin might inhibit UVB-induced photodamage of keratinocytes via inhibiting NLRP3 inflammasomes and activating the PI3K/Akt pathway.

RRx-001 reduces the viability of HCC cells and induces apoptosis. This effect may be due to the downregulation of CD47 expression and the alteration of the TP53 protein regulatory pathway.

P1, N=30, Recruiting, University of Kentucky | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=31, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

CEP70 promotes tumour angiogenesis and metastasis by upregulating VEGFA through NF-κB pathway activation.

Notably, IDET exhibited an improvement in acute peritonitis by inhibiting the activation of NLRP3 inflammasome. Overall, our study highlights the significant anti-inflammatory activity of IDET, providing valuable insights into its therapeutic potential for acute peritonitis.

P2, N=53, Completed, EpicentRx, Inc. | Phase classification: P2a --> P2

P3, N=292, Active, not recruiting, EpicentRx, Inc. | Recruiting --> Active, not recruiting

Using letrozole and a high-fat diet, a PCOS rat model was established, along with a Lipopolysaccharide (LPS) -treated KGN cell inflammation model was established. NF-κB and TERT inhibitors (BAY 11-7082 and BIBR1532) were then administered to LPS-induced KGN cells...LPS-treated KGN cells demonstrated increased expression of inflammatory and pro-apoptotic factors, later restored post-treatment with NF-κB and TERT inhibitors (P are all less than 0.05). In conclusion, TERT may induce granulosa cell apoptosis by participating in the regulation of the NF-κB signaling pathway, thereby mediating the chronic inflammatory response of PCOS through downstream inflammatory factors IL-6 and TNF-α.

In addition to activating NF-κB, the NF-κB inhibitor BAY 11-7082 reduced skatole-induced cell survival and the mRNA expression of IL-6 and TNF-α. NF-κB activation was attenuated by the extracellular signal-regulated kinase (ERK) pathway inhibitor U0126 and the p38 inhibitor SB203580, but not by the c-Jun N-terminal kinase (JNK) inhibitor SP600125...Moreover, the balance between NF-κB and AhR activation appears to govern the skatole-induced increases in IL-6 and TNF-α expression. Therefore, the present findings provide new insights into the mechanisms linking tryptophan-derived gut microbiota metabolites with colorectal disease.

The obtained results suggested the strong interaction between NLRP3 inflammasome and TNBC and revealed that pharmacological inhibition, using NLRP3-specific inhibitor MCC950, and genetic silencing of NLRP3 inflammasome using specific small interfering RNA, reduced inflammatory responses and facilitated PTX-determined tumor cell death. Thus, NLRP3 inflammasome manipulation in combination with anti-tumor drugs opens up new therapeutic perspectives for TNBC therapy.

These protective effects were mediated by down-regulating inflammatory NLRP1, IL-1β, IL-6, and TNF-α, as well as up-regulating antioxidative NRF2, NQO1, GCLC, and PGC-1α, and neuroprotective CREB, BDNF, and BCL2. The study results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenic mechanisms, and indicate the potential use of LM-021 and LM-036 as dual inflammasome inhibitors in treating both NLRP1- and NLRP3-associated PD.

P2, N=394, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

We further revealed that UTI could inhibit NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation by increasing the expression of nuclear factor-κB (IκB) kinase-alpha (IKKα) interacting with apoptosis-associated speck-like protein containing CARD (ASC) to alleviate kidney damage. These findings provide evidence of the renoprotective role of UTI in cardiac surgery-associated (CSA)-AKI, which is associated with the inhibition of NLRP3 inflammasome activation by upregulating IKKα.

P2, N=115, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

HSP70 promotes the EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating the NF-κB pathway.

These findings suggest that MCC950 treatment holds promise for mitigating the proinflammatory state observed in kidneys after BD and CS.

P2, N=31, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Feb 2026 --> Nov 2024 | Trial primary completion date: Feb 2026 --> Oct 2024

P2, N=108, Recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2025 --> Dec 2024 | Trial primary completion date: Mar 2025 --> Dec 2024

P1, N=60, Completed, Hoffmann-La Roche | Trial completion date: Jul 2025 --> Jul 2024 | Trial primary completion date: Jul 2025 --> Jul 2024 | Recruiting --> Completed

SMAD2 and NF-κB p65 were overexpressed and transfected into cells, and the inhibitors SB431542 and BAY 11-7082 were added to block the TGF-β1/Smad and NF-κB pathways, respectively...BBR can significantly inhibit TGF-β1-induced EMT in normal and cancerous colon epithelial cells through the inhibition of the TGF-β1/Smad and NF-κB p65 pathways. TGF-β1/Smads can promote the NF-κB p65 pathway, which is a common target of miR-1269a, and can partially regulate the expression of miR-1269a.

Our findings elucidate the involvement of the NLRP3/PERK/eIF2 axis as a novel driver of AML cell survival. Targeting NLRP3-induced signaling pathways, particularly through the PERK/eIF2 axis, presents a promising therapeutic strategy for AML intervention. These insights into the role of the NLRP3 inflammasome offer potential avenues for improving the prognosis and treatment outcomes of AML patients.

Our study uncovered a novel pathway in platelet activation involving the cPLA2-NF-κB axis, which plays a key role in the antiplatelet effects of eugenol. These findings suggest that eugenol could serve as a valuable and potent prophylactic or therapeutic option for arterial thrombosis.

The inflammatory responses were reversed by NLRP3 inhibitor MCC950 and NF-κB inhibitor Bay11-7082. Additionally, N-acetylcysteine (NAC) blocked the upregulation of the NF-κB/NLRP3 signaling pathway and remarkably alleviated the inflammatory response. These results demonstrated that AMA could induce inflammation through activating the NLRP3 inflammasome triggered by ROS/NF-κB signaling pathway. Our research provides new insights into the molecular mechanism of AMA-induced inflammation damage and may contribute to establish new prevention strategies for AMA hepatotoxicity.

NLRP3 overexpression using NLRP3 cDNA further promoted BC cell malignant progression after LPS stimulation and reversed cryptotanshinone-reduced LPS-induced BC cell malignant behaviors. NLRP3 might possess oncogenic activity in BC, and the antitumor activity of cryptotanshinone in BC in vitro might be related to its inhibition of NLRP3 expression.

P2, N=10, Recruiting, Zomagen Biosciences, Ltd

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Dec 2025 --> Oct 2025 | Trial primary completion date: Nov 2025 --> Sep 2025

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Oct 2024 --> Nov 2025

P1, N=72, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

P1, N=2, Terminated, EpicentRx, Inc. | N=24 --> 2 | Trial completion date: Dec 2024 --> Jul 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Jul 2024; Low Enrollment

In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.

Downregulation of ATP5F1D as a new therapeutic strategy that could mediate pyroptosis via suppressing mtROS/NLRP3/caspase-1/GSDMD pathway to inhibit EC progression.

Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.

HJXJ suppressed pyroptosis and inflammasome activation by inhibiting NLRP3 expression. Generally, HJXJ has the potential to reduce DKD injury and exerts anti-DKD effects by inhibiting the NLRP3-mediated NLRP3 inflammasome activation and pyroptosis in vitro and in vivo.

P1, N=72, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P2, N=81, Completed, Halia Therapeutics, Inc. | Recruiting --> Completed