title: COX inhibitors: a patent review (2011 - 2014).
abstract: BACKGROUND
  The COX enzymes play a central role in the biosynthetic pathway of important biological mediators called prostanoids. Differences in regulation of gene expression, stability of transcripts and proteins determine the different biological functions of COX-1 and COX-2. While the COX-1 gene has been considered to be a 'housekeeping' gene expressed in many tissues and cells, COX-2 gene is upregulated during inflammation, hypoxia and in many cancers.
  
  
  METHODS
  The first part of this review provides a survey of the development of both modified traditional NSAIDs (tNSAIDs) and COX inhibitors (coxibs) with reduced side effects for the treatment of inflammation and cancer. The second part deals with patents reporting several dual inhibitors characterized by the conjugation of a COX-inhibitor scaffold to a molecule able to modulate a different target. Finally, two patents on novel COX inhibitor scaffolds are reported.
  
  
  CONCLUSIONS
  The most interesting branch of research concerns the conjugation of a COX-inhibitor scaffold to a molecule able to modulate a different target, in order to either enhance anti-inflammatory activity or to act as a dual inhibitor. Among the described compounds, selenium-containing coxibs inhibiting COX-2 and Akt, in addition to the multi-target biphenyl derivatives as dual inhibitors of COX and fatty acid amide hydrolase, are the most promising ones.
authors.affiliation: a Sapienza University of Rome, Dipartimento di Chimica e Tecnologie del Farmaco , p.le A. Moro 5, I-00185 Rome, Italy mariangela.biava@uniroma1.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Consalvi
authors.affiliation: a Sapienza University of Rome, Dipartimento di Chimica e Tecnologie del Farmaco , p.le A. Moro 5, I-00185 Rome, Italy mariangela.biava@uniroma1.it.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Biava
authors.affiliation: a Sapienza University of Rome, Dipartimento di Chimica e Tecnologie del Farmaco , p.le A. Moro 5, I-00185 Rome, Italy mariangela.biava@uniroma1.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Poce
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D015195:Drug Design; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D010330:Patents as Topic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: COX; COX inhibitors; NSAIDs; anti-cancer agents; anti-inflammatory agents