Isoform-selective inhibitor binding. The COX-1 and COX-2 active sites are shown superimposed (COX-1, yellow; COX-2, pink). Two inhibitors are seen: flurbiprofen (orange), a nonselective inhibitor, and SC-558 (blue), a COX-2–selective inhibitor. NSAIDs achieve COX inhibition by occupying the upper portion of the active site channel, preventing the fatty acid substrate from gaining access to the active site tyrosine seen at the upper right. Note how the COX-2–selective inhibitor projects leftward into a side pocket that is not exploited by the nonselective inhibitor.