Dual-Target Inhibitors Based on COX-2: A Review from Medicinal Chemistry Perspectives

Abstract

Inhibitors of COX-2 constitute a class of anti-inflammatory analgesics, showing potential against certain types of cancer. However, such inhibitors are associated with cardiovascular toxicity. Moreover, although single-target molecules possess specificity for particular targets, they often lead to poor safety, low efficacy and drug resistance due to compensatory mechanisms. A new generation of dual-target drugs that simultaneously inhibit COX-2 and another target is showing strong potential to treat cancer or reduce adverse cardiac effects. The present perspective focuses on the structure and functions of COX-2, and its role as a therapeutic target. It also explores the current state and future possibilities for dual-target strategies from a medicinal chemistry perspective.

Graphical abstract

Keywords::

• COX-2
• drug design
• dual-target inhibitor
• structure–activity relationship

Supplementary data

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Financial disclosure

This review was supported by National Natural Science Foundation of China (no. 92159302 to W Li), the Science and Technology Project of Sichuan (no. 2022ZDZX0018 to W Li), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (no. ZYGD22009 to W Li). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This review was supported by National Natural Science Foundation of China (no. 92159302 to W Li), the Science and Technology Project of Sichuan (no. 2022ZDZX0018 to W Li), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (no. ZYGD22009 to W Li). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.