P2, N=24, Recruiting, Zydus Lifesciences Limited

Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated apoptosis, autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV infection.

P2, N=210, Recruiting, Shaperon | Not yet recruiting --> Recruiting

P2, N=300, Not yet recruiting, University Hospital, Basel, Switzerland | Initiation date: Nov 2023 --> Apr 2024

Moreover, PLTP could bind to NLRP3 and negatively regulate the activity of the NLRP3 inflammasome/GSDMD signal pathway. This study demonstrated that PLTP can ameliorate SICD by inhibiting inflammatory responses and cardiomyocyte pyroptosis by blocking the activation of the NLRP3 inflammasome/GSDMD signaling pathway.

Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells...In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

P2, N=216, Recruiting, EpicentRx, Inc. | Not yet recruiting --> Recruiting

Pip ameliorates NASH progression, and the therapeutical effect was associated with inhibition of hepatocyte pyroptosis induced by NF-κB.

By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

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

P3, N=18, Terminated, EpicentRx, Inc. | Trial completion date: Aug 2022 --> Mar 2024

P1, N=24, Active, not recruiting, EpicentRx, Inc. | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

The use of RRx-001 with the function of downregulating the expression of innate immune checkpoint molecule CD47 provides a powerful means for treating advanced HCC containing a substantial proportion of immunosuppressive macrophages...Combined with the ROS generation and an upregulated "eat me" signal level of DOX, BEA-D@R collectively increased RNS generation, enhanced T cell infiltration, and maximized macrophage phagocytosis, leading to an average of 40% tumor elimination in a mice model bearing an initial tumor of approximately 300 mm3 that mimics advanced HCC. Overall, this study uncovered the "all-in-one" immunotherapeutic functionalities of a clinical translatable nanoplatform for enhanced immunotherapy of advanced HCC.

In comparison to the existing anti-inflammatory drug, dexamethasone, and triterpenoid saponin Rk1, DT-13 more efficiently inhibits inflammation in the applied cell culture model. Therefore, DT-13 may serve as a lead compound for the development of new more effective anti-inflammatory drugs with minimised side effects.

P2, N=7, Completed, Zomagen Biosciences, Ltd | Recruiting --> Completed | Phase classification: P2a --> P2 | N=10 --> 7 | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Oct 2023 --> Mar 2024

Additionally, when coupled with H6, a small peptide targeting MDSCs, Au NPs demonstrated the capacity to effectively reduce IL-1β levels and diminish the MDSCs population in tumor microenvironment, leading to enhanced T cell activation and increased immunotherapeutic efficacy in mouse tumor models that are sensitive and resistant to PD-1 inhibition. Our findings unraveled a novel approach wherein peptide-modified Au NPs relieved the suppressive impact of the tumor microenvironment by inhibiting MDSCs-mediated IL-1β release, which is the first time reported the employing a nanostrategy at modulating MDSCs to reverse the immunosuppressive microenvironment and may hold promise as a potential therapeutic agent for cancer immunotherapy.

Meanwhile, TLR4 inhibitor BAY11-7082 might overturn the repression effect of TLR4 on M.tb-infected HTP-1 cell damage. YY1-activated TLR4 might aggravate mycobacterial injury in human macrophages after M.tb infection by the NF-kB pathway, providing a promising therapeutic target for TB treatment.

Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKβ expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1β production, potentially ameliorating pain management in BCP.

P1, N=5, Recruiting, University of Kentucky | Not yet recruiting --> Recruiting

BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.

P2, N=216, Not yet recruiting, EpicentRx, Inc. | Initiation date: Dec 2023 --> Apr 2024

Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels...Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.

P2, N=28, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Gout flare involves multiple inflammatory mediators that may be used as potential therapeutic targets.

P2, N=80, Recruiting, Halia Therapeutics, Inc. | Not yet recruiting --> Recruiting

P2, N=2, Terminated, Olatec Therapeutics LLC | N=10 --> 2 | Recruiting --> Terminated; The study was terminated due to study design issues that did not allow for determination of efficacy and safety in subjects with Schnitzler Syndrome who are currently well controlled on anakinra therapy.

P2, N=80, Not yet recruiting, Halia Therapeutics, Inc.

Metformin can inhibit the expression of NLRP3 inflammasome, thereby suppressing the expression of inflammation-related factors, reducing the damage of the inflammatory microenvironment to normal cells, and delaying the progression of colorectal cancer.

Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.

The activity of RelA and NF-κBp50 was assessed and confirmed using Bay 11-7082...The GNP suppressed IL-6 overexpression and secretion by deactivating NF-κBp65/NF-κBp50 transcription activity and upregulating miR-26a-5p expression in activated BC cells. These findings suggest that GNP have potential as a therapeutic intervention for BC by targeting IL-6 expression and associated pathways.

In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1β and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment.

The experimental results showed that Mel reduced the myocardial infarction area, decreased aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and significantly inhibited the expression of reactive oxygen species (ROS), NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), but its effect on superoxide dismutase (SOD) was opposite. Therefore, Mel may improve autophagy and inflammation during myocardial ischemia/reperfusion and may decrease myocardial cell damage by inhibiting NLRP3.

Curcumin improves endothelial cell injury in atherosclerosis by inhibiting the expression of NLRP3 inflammatory bodies.

This was confirmed using an NLRP3 inhibitor, OLT1177, which revealed a similar beneficial effect in combating TNBC progression. Sch B treatment also inhibits IL-1β-induced EMT expression of TNBC cells, which may contribute to the anti-tumor response.

Our results suggest that LDHA and its major metabolite lactate drive NPC progression by regulating TAK1 and its downstream NF-κB signaling, which could become a therapeutic target in NPC.

First, human oral mucosal fibroblasts (HOMFs) were cultured, an OSF model was established using arecoline, and APN and Imiquimod treatment were administered. In vivo experiments further confirmed that APN ameliorated OSF in mice by inhibiting ROS/NLRP3 inflammatory pathway. In conclusion, APN ameliorated arecoline-induced OSF by promoting FOXO3A expression and downregulating the ROS/NLRP3 pathway.

P1, N=80, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

An X-ray structure of NP3-562 bound to the NLRP3 NACHT domain revealed a unique binding mode as compared to the known sulfonylurea-based inhibitors. In addition, NP3-562 shows also a good overall development profile.

In vivo studies show that ENB has a significant ameliorative effect on mouse models of NLRP3 inflammasome-related diseases, including lipopolysaccharide (LPS)-induced systemic inflammation, monosodium urate (MSU)-induced peritonitis, and high-fat diet (HFD)-induced type 2 diabetes (T2D). These data show that ENB is a targeted inhibitor of NEK7 with strong anti-NLRP3 inflammasome activity, making it a potential candidate drug for the treatment of inflammasome-related diseases.

Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.

P2, N=28, Not yet recruiting, Novartis Pharmaceuticals | Phase classification: P2a --> P2

Notch1 pathway was overactivated in podocytes of LN patients and MRL/lpr mice. Blockade of Notch1 pathway reduced renal inflammation and alleviated podocyte injury via inhibition of NLRP3 inflammasome activation in LN.