MK-0966 - a highly selective COX II-inhibitor

Journal/Book: Z Rheumatol 1998; 57: 177. 1998;

Abstract: Dr. C.-C. Chan; Merck Frosst Centre for Therapeutic Research Kirkland Quebec It is now well established that there are two major isoforms of cyclooxygenase (COX). The constitutive enzyme COX-1 has been well characterized and is postulated to be involved in the maintenance of essential physiological functions such as platelet aggregation cytoprotection in the stomach and maintenance of normal kidney functions. A second isozyme COX-2 has also been described and it shares about 60 % sequence homology with COX-1 at the amino acid level. COX-2 has been shown to be induced significantly in vivo under inflammatory conditions. This has led to the concept that COX-1 serves a physiological homeostatic function whereas COX-2 plays a key role in pathological conditions. This has led to the concept that COX-1 serves a physiological homeostatic function whereas COX-2 plays a key role in pathological conditions. This has also provided a rationale for the development of selective inhibitors of COX-2 as a new class of anti-inflammatory agents which would possess a substantially improved side effect profile (e. g. markedly reduced propensity for gastrointestinal erosions) compared to current clinically available non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit both COX-1 and COX-2. At present selective COX-2 inhibitors such as MK-0966 are available and preclinical studies have shown that inhibition of COX-2 alone by these compounds is sufficient to achieve anti-inflammatory antipyretic and anti-algesic effect without gastrointestinal toxicity consistent with the COX-2 hypothesis. Initial clinical studies with MK-0966 characterized in vitro as a highly selective inhibitor of COX-2 were designed to test the COX-2 hypothesis. ... le

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