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It's well-known that COX-2 selectivity is generated by one amino acid substitution of isoleucine at position 523 in COX-1 with valine in COX-2, while the smaller Val523 residue in COX-2 opens up an 17% extra space, namely side pocket in the enzyme, which allows large molecules to pass into the entrance of COX-2 channel (Gierse et al.
Increasing degrees of COX-2 selectivity are associated with augmented cardiovascular risk.
Etodolac, the active ingredient in Lodine, has already demonstrated COX-2 selectivity based on several comparative and large-scale safety studies.