P3, N=120, Not yet recruiting, Emory University

P4, N=130, Recruiting, Montefiore Medical Center | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P=N/A, N=120, Active, not recruiting, Johns Hopkins University | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P3, N=136, Completed, Laboratorios Silanes S.A. de C.V. | Recruiting --> Completed | Trial completion date: Jul 2025 --> Dec 2025

P3, N=89, Completed, Laboratorios Silanes S.A. de C.V.

Rats were administered OANG (high/low dose) intra-articularly, with celecoxib as a positive control...Furthermore, OANG ameliorated hippocampal oxidative stress and inflammation (decreased Cleaved caspase-3, Malondialdehyde; increased IL-10). Network pharmacology and docking suggested the involvement of peroxisome proliferator-activated receptor gamma, mitogen-activated protein kinase 3, prostaglandin-endoperoxide synthase 2, and pathways such as estrogen signaling and cyclic adenosine monophosphate signaling.

In contrast, NRF2 activators, such as bardoxolone methyl (CDDO-Me), sulforaphane, and dimethyl fumarate, exhibit chemopreventive effects by enhancing detoxification and mitigating oxidative DNA damage during early tumorigenesis...Therefore, understanding the temporal and contextual effects of NRF2 signaling is crucial for therapeutic design. The aim of this review is to examine how pharmacological modulation of NRF2 influences the invasive and metastatic dimensions of tumor progression, in addition to discussing its potential integration into TNM-based prognostic and treatment frameworks.

Similarly, subcutaneous KEAP1 KO tumors were larger and more immune-suppressed compared to WT tumors. Both CDDO-Me and omaveloxolone reduced the tumor burden and improved immune cell phenotypes within the TIME independent of KEAP1 mutational status.

This study investigates the in vitro antitumor properties and mechanism of action of novel vicinal diaryl-substituted heterocyclic COX-2 inhibitors, with a focus on VA1213, in comparison to celecoxib, a widely marketed COX-2 inhibitor known for its off-target effects...Its ability to interfere with multiple cancer-associated signaling pathways and reduce tumor cell aggressiveness underscores its potential as a promising therapeutic candidate. Further in vivo studies are warranted to confirm its efficacy and assess potential off-target effects.

Docking analysis results demonstrated that compounds 1, 2, 4, and 5 had the capacity to occupy the catalytic domain of COX-2 enzymes, exhibiting analogous binding conformations to those observed with the selective COX-2 inhibitor celecoxib. All these findings implied that these di/trinormonoterpenoid glucosides derived from PC possess promising characteristics for development as novel COX-2-targeted therapeutic agents.

RNA-seq analysis was also utilised to highlight the molecular mechanisms underpinning the effects DOX in AC16 cells and the CDDO-mediated mitigation of cardiotoxicity. This study provides novel insight into NRF2 dynamics in the widely utilised AC16 cells whilst further elucidating the molecular mechanisms contributing to DOX cardiotoxicity and potential NRF2-orchestrated defence.

P2, N=4, Completed, Leidos Life Sciences | Active, not recruiting --> Completed | N=2000 --> 4