Abstract
The recent marketing of two selective cyclooxygenase-2 (COX-2) inhibitors, celecoxib and rofecoxib is remarkable considering that COX-2 was only discovered eight years ago as a growth factor- and cytokine-inducible gene. Concomitant with these pharmaceutical successes is the advances in our understanding of the molecular and structural basis for selective COX-2 inhibition. This review provides a perspective on the ongoing structure-activity relationship (SAR) efforts in the search of COX-2-specific inhibitors with particular reference to their structural basis for isozyme-specific inhibition. In addition to the existing inhibitor classes, this review will also highlight many novel structural classes which have recently emerged due to a better understanding of the active site differences between the two isozymes with a special emphasis on the modification of the well-established non-steroidal anti-inflammatory drug (NSAID) scaffold. In addition to its role in inflammation, recent studies suggest that COX-2-derived prostaglandins may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. In this review, we summarize the NSAID epidemiological evidence, studies demonstrating overexpression of COX-2 in multiple human tumors and pharmacological evidence in animal models, which indicate that COX-2 inhibitors could be used in the prevention or treatment of a broader range of disease.
Keywords: Cyclooxygenase-2 Inhibitors, Non-Ulcerogenic, Anti-Inflammatory, Anti-Cancer Agents, Growth factor, Cytokine-inducible gene, COX-2 specific inhibitors, Human Tumors, Acidic sulfonamides
Current Drug Targets
Title: Discovery and Design of Selective Cyclooxygenase-2 Inhibitors as Non-Ulcerogenic, Anti-Inflammatory Drugs with Potential Utility as Anti-Cancer Agents
Volume: 2 Issue: 1
Author(s): Amit S. Kalgutkar and Zhiyang Zhao
Affiliation:
Keywords: Cyclooxygenase-2 Inhibitors, Non-Ulcerogenic, Anti-Inflammatory, Anti-Cancer Agents, Growth factor, Cytokine-inducible gene, COX-2 specific inhibitors, Human Tumors, Acidic sulfonamides
Abstract: The recent marketing of two selective cyclooxygenase-2 (COX-2) inhibitors, celecoxib and rofecoxib is remarkable considering that COX-2 was only discovered eight years ago as a growth factor- and cytokine-inducible gene. Concomitant with these pharmaceutical successes is the advances in our understanding of the molecular and structural basis for selective COX-2 inhibition. This review provides a perspective on the ongoing structure-activity relationship (SAR) efforts in the search of COX-2-specific inhibitors with particular reference to their structural basis for isozyme-specific inhibition. In addition to the existing inhibitor classes, this review will also highlight many novel structural classes which have recently emerged due to a better understanding of the active site differences between the two isozymes with a special emphasis on the modification of the well-established non-steroidal anti-inflammatory drug (NSAID) scaffold. In addition to its role in inflammation, recent studies suggest that COX-2-derived prostaglandins may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. In this review, we summarize the NSAID epidemiological evidence, studies demonstrating overexpression of COX-2 in multiple human tumors and pharmacological evidence in animal models, which indicate that COX-2 inhibitors could be used in the prevention or treatment of a broader range of disease.
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Cite this article as:
Kalgutkar S. Amit and Zhao Zhiyang, Discovery and Design of Selective Cyclooxygenase-2 Inhibitors as Non-Ulcerogenic, Anti-Inflammatory Drugs with Potential Utility as Anti-Cancer Agents, Current Drug Targets 2001; 2 (1) . https://dx.doi.org/10.2174/1389450013348830
DOI https://dx.doi.org/10.2174/1389450013348830 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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