celecoxib

Overview

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor belonging to the nonsteroidal anti-inflammatory drug (NSAID) class, distinguished by its preferential blockade of the inducible COX-2 isoform over the constitutively expressed COX-1. By inhibiting COX-2, celecoxib suppresses the enzymatic conversion of arachidonic acid to prostaglandin H2, thereby reducing downstream synthesis of prostaglandin E2 (PGE2) and other pro-inflammatory eicosanoids. This mechanism underlies its well-established clinical use in managing pain, osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Compared to non-selective NSAIDs such as (RS)-ketoprofen or sulindac, celecoxib's COX-2 selectivity is associated with a reduced risk of gastrointestinal ulceration, making it a widely used reference compound in anti-inflammatory research. In preclinical and translational settings, its inhibition of the COX-2/PGE2 axis also positions it as a candidate for modulating neuroinflammation, cancer-related inflammation, and chemotherapy-induced adverse effects.

Beyond its canonical anti-inflammatory role, celecoxib has attracted growing interest as an oncological adjunct and a neurological therapeutic. Its ability to suppress proinflammatory cytokine signaling — including pathways involving TNF-α and interleukin-6 (IL-6) — and to downregulate Prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2) expression at the transcriptional level has prompted investigation into its utility across a remarkably broad spectrum of diseases. The drug's well-characterized pharmacology and decades of clinical safety data make it a frequent positive control and benchmark comparator in studies evaluating novel anti-inflammatory and antitumor agents.

Focus of Latest Publications

Recent publications have continued to examine celecoxib as a cyclooxygenase-2 (COX-2) inhibitor in both mechanistic and translational settings. In a randomized crossover pharmacokinetic study in healthy volunteers, 8 days of celecoxib pretreatment modestly inhibited tramadol bioactivation, reducing formation of O-desmethyltramadol without changing tramadol exposure, while pharmacological effects were reported as negligible. This work supports a potential drug–drug interaction involving CYP2D6-mediated metabolism. Celecoxib was also evaluated in a rat model of paclitaxel-induced peripheral neuropathy, where it attenuated thermal and mechanical hypersensitivity, improved histological injury in dorsal root ganglia, sciatic nerve, and plantar skin, and downregulated COX-2, prostaglandin E2, and MHC expression; in vitro, it reduced neuronal apoptosis and promoted survival through COX-2/PGE2 signaling.

Several studies used celecoxib as a comparator or reference standard in anti-inflammatory and anticancer screening. In vitro and in silico work on novel pyrimidines, thiadiazoles, and methoxylated diarylpyrazoles compared their COX-2 inhibitory and anti-inflammatory activities with celecoxib, with some candidates showing equal or greater potency, selectivity, or cytokine suppression than celecoxib. Similarly, a study of Convolvulus oxyphyllus extracts and selenium nanoparticles reported downregulation of IL6 and COX2 expression comparable to celecoxib, alongside docking results against COX-2 and IL-6. In a separate cancer-focused study, sulindac-celecoxib Janus dendrimers showed selective growth inhibition against MCF-7 cells, indicating that celecoxib-containing conjugates may contribute to anticancer activity.

Celecoxib also appeared in combination-based therapeutic strategies. A spatiotemporally programmed nanovesicle delivering celecoxib and a gemcitabine prodrug was designed for triple-negative breast cancer; the system released celecoxib first to suppress local prostaglandin E2 signaling and then triggered delayed gemcitabine activation, boosting dendritic cell maturation and antitumor immunity while inhibiting primary tumor growth and metastasis in models. In amyotrophic lateral sclerosis, celecoxib was part of PrimeC, a fixed-dose oral combination with ciprofloxacin intended to target neuroinflammation, iron homeostasis, and dysregulated microRNAs. Another clinical study examined celecoxib combined with low-dose-rate brachytherapy in prostate cancer, focusing on long-term oncological outcomes and quality of life, although the abstract provided only the study aim rather than results.

Key Publications

• NEWJul Effects of Celecoxib and Etoricoxib on the Pharmacokinetics and Pharmacological Effects of Orally Administered Tramadol: A Randomised Controlled Trial. (Basic & clinical pharmacology & toxicology, 2026, PMID 42272128): "Celecoxib has been reported to act as a weak inhibitor of CYP2D6 in vivo."
• Jun Spatiotemporally programmed nanomedicine engineering to resolve conflicting immunosignals in triple-negative breast cancer. (Signal transduction and targeted therapy, 2026, PMID 42236688): "Following preferential accumulation in tumor tissue, enzymatic disassembly of the nanomedicine triggers the rapid release of celecoxib to suppress local PGE2 signaling and alleviate immune suppression."
• May Anticancer activity of fluoxetine Janus dendrimer against cancer cells. (Artificial cells, nanomedicine, and biotechnology, 2026, PMID 42167254): "We evaluated the in vitro anticancer effects of sulindac, ketoprofen, celecoxib and the antidepressant fluoxetine, both free and coupled with synthesized dendrons and dendrimers, on the proliferation and apoptosis of human MCF-7 (human mammary adenocarcinoma), SKLU-1 (human lung adenocarcinoma) and as a control the normal monkey kidney (COS-7) cell line."
• May Biogenic selenium extract-mediated and total Convolvulus oxyphyllus extracts suppress IL6 and COX2 expression: insights from LC-MS metabolite profiling and molecular docking. (Scientific reports, 2026, PMID 42128884): "Both extract-mediated Se-NPs and total alcohol extract significantly down-regulated IL6 and COX2 expression (69% and 73%, respectively), comparable to Celecoxib."
• May Balancing Efficacy and Safety: Discovery and Biological Activity Evaluation of Novel Nitrogen-Containing Fused Heterocyclic Cyclooxygenase Inhibitors. (Journal of medicinal chemistry, 2026, PMID 42093605): "Combining virtual screening and structure-based design, we identified compounds 19, 39, 70, and 73 as the most promising analogues, surpassing celecoxib in both COX-2 (IC50 17.4-31.1 nM; vs celecoxib: 59 nM) and COX-1 inhibition (IC50 26.4-43.8 nM; vs celecoxib: 1455 nM)."
• May Celecoxib Mitigates Paclitaxel-Induced Peripheral Neuropathy Through Modulation of the COX-2/PGE2 Pathway in Rats. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42048120): "This study explored celecoxib's therapeutic efficacy against paclitaxel-induced neuropathy in rats via the COX-2/PGE2 pathway."
• Mar Methoxylated 3,4-diaryl-5-methyl-1(H)-pyrazoles: discovery of a new anti-inflammatory scaffold. (Bioorganic chemistry, 2026, PMID 41894851): "The anti-inflammatory activity of the trimethoxylated analog 3r reached 90% inhibition and surpassed that of celecoxib."
• Apr Safety and Efficacy of PrimeC in Amyotrophic Lateral Sclerosis: The PARADIGM Randomized Clinical Trial. (JAMA neurology, 2026, PMID 41837970): "PrimeC is a fixed-dose oral combination of celecoxib and ciprofloxacin designed to target ALS-related mechanisms, including neuroinflammation, iron homeostasis, and dysregulated microRNAs."
• Jun Design, synthesis, in vitro, and in silico evaluation of multi-functionalized pyrimidines as potential multitarget-directed anti-inflammatory agents. (Bioorganic chemistry, 2026, PMID 41806609): "...with comparisons made to the well-known COX inhibitors celecoxib and diclofenac sodium."
• May Novel thiadiazole derivatives: synthesis, in silico, in vitro and in vivo evaluation of analgesic and anti-inflammatory activities. (Bioorganic chemistry, 2026, PMID 41638094): "Based on docking scores comparable to celecoxib, three compounds (4d, 4e, 4f) were selected for in vivo pharmacological testing."