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.