Cyclooxygenase-2 inhibitors clinical development

Tenidap (Figure 8.26) is a dual cyclooxygenase (COX) and 5-lipoxygenase (5-LPO) inhibitor developed as an anti-inflammatory agent. Severe abnormalities in hepatic function were reported in Japanese clinical trials [28]. Although the thiophene is not directly implicated in these findings, the ready activation of this system to potential reactive metabolites may be suggestive of the involvement of this function. 

Individuals with inherited familial adenomatous polyposis (FAP) develop numerous polyps, the premalignant precursors to colorectal carcinoma. A remarkable heterogeneity in patient response was observed in a clinical trial with a cyclooxygenase-2-inhibitor, celocoxib, which is known to be efficacious in FAP. SELDl proteomic profile revealed that a putative marker at 16,961.4 Da was a strong discriminator between response and nonresponse [134]. 

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