The synthesized compounds were screened for their anti-inflammatory and antioxidant potential using selective COX-2 inhibitory activity and DPPH assays compared to celecoxib and ascorbic acid, respectively...Compound 9 additionally modified the histological alterations caused by gamma irradiation-induced tubular epithelial cell necrosis. Accordingly, compound 9 can help to reduce the adverse effects of irradiation.

Celecoxib effectively inhibited lung-carcinoma development, inflammation, and emphysema, demonstrating the potential for chemoprevention in smokers and patients with COPD. Further studies on EP4 inhibitors for the prevention of emphysema and lung cancer are warranted.

P3, N=192, Completed, Laboratorios Silanes S.A. de C.V. | Recruiting --> Completed

P4, N=72, Completed, Qilu Hospital of Shandong University; Qilu Hospital of Shandong University

P=N/A, N=60, Not yet recruiting, Southern Medical University Southern Hospital; Southern Medical University Southern Hospital

P=N/A, N=84, Completed, Haydarpasa Numune Training and Research Hospital | Recruiting --> Completed | Trial completion date: Aug 2024 --> Feb 2025 | Trial primary completion date: Aug 2024 --> Feb 2025

P3, N=224, Completed, Yangtze River Pharmaceutical Group Co., Ltd.

Celecoxib significantly inhibited clinical arthritis and bone progression in the joints of SKGc, but not etoricoxib (another COX-2i), nor naproxen (COX-2 nonselective). Of the NSAIDs, only celecoxib inhibited bone progression in SKGc and OB differentiation and bone mineralization in the BdCs of mice and AS patients via CDH11/WNT signaling, independent of the COX-2 inhibition. [BMB Reports 2025; 58(3): 140-145].

P1, N=20, Completed, Yangtze River Pharmaceutical Group Co., Ltd.

P=N/A, N=500, Recruiting, University of Utah | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Jul 2025 --> Jul 2027

Additionally, compound 52 showed significant synergy with celecoxib, a selective COX2 inhibitor, both in vitro and in vivo. Our data suggest that compound 52 is a promising candidate for further development in KRAS-mutated cancers.

These COX inhibitors are used to reduce the symptoms of inflammation, with aspirin, indomethacin or flurbiprofen being prominent examples. Celecoxib-based compound 10 showed an IC50 value in the sub-µM range for COX-2 and in contrast to its ortho-carborane derivative a reversed selectivity preference for COX-2 instead of COX-1. While none of these carborane derivatives outperformed their organic analogues, the flurbiprofen-based nido-carborane derivatives 14a and 14b surpassed the known carborane-based flurbiprofen analogues.

Ortho ester bond-coupled sulindac dimer (SU-OE) was first synthesized and co-assembled with doxorubicin to obtain pH-sensitive nanodrug (SU-OE@DOX NPs). In vivo imaging results demonstrated that the nanoparticles could be enriched at tumor site and could raise the temperature of the tumor area to 56.7 °C under NIR laser irradiation. The released SU from HM@I/NPs can inhibit the expression of COX-2, and finally enhanced the chemo-PTT synergistic anti-tumor effect.

Celecoxib (CLX), a potent non-steroidal anti-inflammatory drug, is widely used in pain management...Oral administrations of TQ and CLX at a same dose of 10.00 mg kg-1 alleviated paw lifting number (spontaneous pain) and paw withdrawal threshold evoked by von Frey filaments on metal mesh floor, improved the decreased contents of serum total anti-oxidant capacity and superoxide dismutase, and restored the increased levels of serum malondialdehyde and tumor necrosis factor-alpha. The results suggested that TQ by employing anti-oxidant and anti-inflammatory mechanisms, might relieve the pain induced by hind paw plantar incision, being comparable with CLX.

Thus, intermittent low-dose ERL + SUL treatment enhances tumor-associated MHC expression and remodels the immune cell niche toward a more permissive "helper" immune microenvironment. We conclude that early immune-interception strategies targeting interferon-γ signaling may benefit FAP patients at drug doses below the clinical standard of care.

The treatment regime was ineffective in suppressing SARS-CoV-2 infection in K18-hACE2 mice. Overall, animal studies demonstrated the protective age- and sex-dependent antiviral efficacy of DFMO and Sulindac against SARS-CoV-2.

P2, N=243, Completed, Heron Therapeutics | Phase classification: P2b --> P2

P2, N=285, Completed, Heron Therapeutics | Phase classification: P2b --> P2

P3, N=231, Recruiting, Laboratorios Silanes S.A. de C.V.

P3, N=72, Recruiting, Laboratorios Silanes S.A. de C.V.

P3, N=136, Recruiting, Laboratorios Silanes S.A. de C.V.

Additionally, supplementation with ATB346, a novel H2S-donating naproxen derivative, prevented AAA development in mice. These studies suggest that SENP3-mediated CTH deSUMOylation regulates macrophage ferroptosis and AAA development. The SENP3/CTH axis is therefore an important therapeutic target for aortic aneurysmal diseases.

Our research discloses that combining laser therapy with celecoxib could serve as an effective therapeutic approach to inhibit BC invasion and metastasis by targeting the EMT process and decelerating disease progression. Further investigations are essential to validate these results in clinical environments.

Notably, cadherin 11 (CDH11), a specific marker for hybrid EMT cells, may exert its regulatory role in cellular function by interfering with branched-chain amino acids (BCAA) metabolism by inhibiting branched-chain ketoacid dehydrogenase to activate the mammalian target of the rapamycin pathway, thus making it a potential therapeutic target for SACC. Overall, these findings suggest a promising treatment strategy that targets hybrid EMT cells to mitigate lung metastasis in SACC. Celecoxib may serve as a promising clinical intervention for the treatment of lung metastases in patients with SACC.

Ibuprofen and celecoxib primarily exert their antidepressant effects through targets and pathways related to inflammation, neural signaling, and cancer, with celecoxib showing a stronger potential antidepressant effect. The expression difference of the core target ALB between depression and healthy individuals further supports the potential effect of the drug on DD. Our findings propose new treatment strategies, support the link between inflammation and depression, and encourage reassessing existing medications for depression.

P1, N=30, Completed, New Approaches to Neuroblastoma Therapy Consortium | Active, not recruiting --> Completed

Cotreatment with celecoxib effectively diminished these changes induced by PGE2...STAT3 inhibitor napabucasin also inhibited COX-2 expression both in the presence and absence of IFN-γ...HH044 treatment also significantly reduced tumor PGE2 levels in vivo. Our study demonstrates the positive feedback loop linking nNOS-mediated NO signaling to the COX-2/PGE2 signaling axis in melanoma, which further potentiates the pro-tumorigenic activity of IFN-γ.

Bardoxolone also exerts great activity to suppress TNBC tumor growth in vivo but does not show toxicity. Therefore, we reveal that the TRIP13/STAT3 circuit promotes TNBC cell proliferation and this circuit is a promising target for the treatment of TNBC.

P2, N=13, Terminated, University of Utah | N=60 --> 13 | Suspended --> Terminated; Insufficient funding

Moreover, the in vitro cytotoxicity study revealed decreased IC50 value in case of the dual drug-loaded NPs compared to all treated groups, with significant decrease in the expression levels of cyclin D1, COX-2, p-Src and FAK proteins, besides, increased caspase-3 level. The findings suggest that DAS/CXB-loaded BSA NPs could serve as a drug delivery platform with increased antitumor effectiveness.

All the novel compounds were screened for their anti-proliferative activity towards breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and lung cancer cell line (A-549) utilizing celecoxib, erlotinib and osimertinib as standards. Cell cycle analysis recorded that exposure of MFC-7 cells to compound 14g resulted in a significant increase in the percentage of cells at the G2/M to 39.15 % compared to the standard erlotinib (9.87 %). Docking study of the most potent candidates 14b, 14g and 14k within COX-2, EGFRWT and EGFRT790M active regions was conducted to suggest the binding mode of these compounds inside these target enzymes.

Downregulation of glutathione and activation of CCND2 signaling pathway caused HSC-3 OSCC cell death. Henceforth, present findings offer an advanced drug delivery method for targeted chemotherapy in treating OSCC.

P2, N=300, Recruiting, Allodynic Therapeutics, Inc | Not yet recruiting --> Recruiting | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Jul 2026 --> Dec 2026

P4, N=442, Completed, Affiliated Hospital of Southwest Medical University; Affiliated Hospital of Southwest Medical University | Not yet recruiting --> Completed

P=N/A, N=60, Completed, West China Hospital, Sichuan University; West China Hospital, Sichuan University | Recruiting --> Completed

P4, N=900, Recruiting, University of Michigan | Not yet recruiting --> Recruiting | Trial completion date: Jan 2030 --> Oct 2027 | Trial primary completion date: Jan 2030 --> Oct 2026

These therapeutic effects were achieved through the modulation of oxidative stress, inflammation, augmentation of antioxidant defenses (including Nrf2 activation), support for cell survival pathways (via PI3K/Akt signaling), regulation of MAPK, mitigation of fibrosis (TGF-β), and preservation of ovarian reserve (as evidenced by AMH, FSH/LH, and estrogen levels). ETO-NLC shows promise as an effective strategy for attenuating radiation-induced ovarian damage, highlighting the need for further research to enhance therapeutic interventions aimed at preserving ovarian function during cancer treatment.

P2, N=59, Completed, Bateman Horne Center | Recruiting --> Completed | Trial primary completion date: Aug 2024 --> Oct 2024

P3, N=100, Completed, Axsome Therapeutics, Inc. | Recruiting --> Completed

P=N/A, N=80, Yongchuan Hospital affiliated to Chongqing Medical University; Yongchuan Hospital affiliated to Chongqing Medical University

P=N/A, N=200, Completed, NanJing First Hospital; NanJing First Hospital

Warm needle therapy guided by ultrasound, in combination with meloxicam, significantly improves pain relief, physical function, inflammatory modulation, and patient satisfaction in KOA patients.