Unveiling Celecoxib from Discovery to Clinical Applications: Insights from ADMET Predictions

Abstract

Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor belonging to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), widely prescribed for the treatment of pain and inflammatory disorders such as osteoarthritis and rheumatoid arthritis. By preferentially inhibiting COX-2 while sparing cyclo-oxygenase-1 (COX-1) at therapeutic doses, celecoxib reduces the synthesis of pro-inflammatory prostaglandins with minimal effects on platelet aggregation, explaining its improved gastrointestinal safety profile compared with nonselective NSAIDs. To further rationalize its pharmacological profile and expand its potential, this study presents a comprehensive in silico ADMET and toxicity evaluation of celecoxib (a) and its key derivatives: parecoxib (b), valdecoxib (c), and etoricoxib (d). Computational predictions demonstrate exceptional drug-likeness across all four compounds, highlighted by zero violations of Lipinski's and Veber's rules and high gastrointestinal absorption. Blood-brain barrier (BBB) penetration analysis reveals that only valdecoxib exhibits potential CNS permeability, whereas the other derivatives remain restricted. Furthermore, acute toxicity assessments (LD50) highlight a favorable safety profile, classifying etoricoxib as the least toxic (Class 6), while celecoxib falls into Class 4. Ultimately, these predictive insights provide a robust theoretical foundation for ongoing pharmacological optimization and pave the way for future biomimetic applications using coordination chemistry.