Ad
related to: selective cyclooxygenase-2 inhibitors
Search results
Results From The WOW.Com Content Network
The inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of the selective COX-2 inhibitor celecoxib. However, with regard to this drug's promise for the therapy of advanced cancers, it is unclear whether the inhibition of COX-2 plays a dominant role, and this has become a controversial and intensely researched issue.
DuP-697 was a building-block for synthesis of COX-2 inhibitors and served as the basic chemical model for the coxibs that are the only selective COX-2 inhibitors on the market today. DuP-697 is a diaryl heterocycle with cis-stilbene moiety. Structure activity relationship (SAR) studies for diaryl heterocyclic compounds have indicated that a cis ...
There are at least two different cyclooxygenase isozymes: COX-1 (PTGS1) and COX-2 (PTGS2). Aspirin is non-selective and irreversibly inhibits both forms [4] (but is weakly more selective for COX-1 [5]). It does so by acetylating the hydroxyl of a serine residue at the 530 amino acid position. [6]
The smaller Val 523 residue in COX-2 allows access to a hydrophobic side-pocket in the enzyme (which Ile 523 sterically hinders). Drug molecules, such as DuP-697 and the coxibs derived from it, bind to this alternative site and are considered to be selective inhibitors of COX-2. [2]
Rofecoxib is a selective COX-2 inhibitor, or "coxib". Though the class of coxibs includes several agents, degrees of COX-2 selectivity vary among them, with celecoxib (Celebrex) being the least COX-2 selective, and rofecoxib (Vioxx), valdecoxib (Bextra), and etoricoxib (Arcoxia), being highly COX-2 selective. [10]
On the other hand, PTGS2 (COX-2) is a more important source of prostaglandins, particularly prostacyclin which is found in blood vessel lining. Prostacyclin relaxes or unsticks platelets, so selective COX-2 inhibitors (coxibs) increase risk of cardiovascular events due to clotting. [26]
Etoricoxib, sold under the brand name Arcoxia, is a selective COX-2 inhibitor developed and commercialized by Merck.It is approved in 63 countries worldwide as of 2007, except the United States where the Food and Drug Administration sent a Non Approvable Letter to Merck and required them to provide additional data.
Etodolac is 179 times more selective at blocking COX-2 than COX-1. [4] Unlike rofecoxib, both etodolac and celecoxib can fully inhibit COX-1 and are designated as having "preferential selectivity" toward COX-2. The R-enantiomer of etodolac is inactive against COX enzymes, but inhibits beta-catenin levels in hepatoma cells. [5]