5-lipoxygenase and cyclooxygenase-2 (5-LOX/COX-2)

5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are critical enzymes that catalyze the conversion of arachidonic acid into potent inflammatory mediators: leukotrienes and prostaglandins, respectively (Source: UniProt P09917, P35354). COX-2 is an inducible enzyme that plays a central role in pain and inflammation, while 5-LOX produces leukotrienes that contribute to vascular permeability and leukocyte recruitment (Source: StatPearls, "NSAIDs"). The therapeutic rationale for targeting both enzymes simultaneously is to achieve superior anti-inflammatory efficacy while mitigating the "shunting" effect. This effect occurs when the inhibition of the COX pathway alone leads to an overproduction of leukotrienes, which can cause gastrointestinal damage or respiratory issues like aspirin-induced asthma (Source: PubMed PMID: 11739831). Dual 5-LOX/COX-2 inhibitors, such as Licofelone, are designed to provide the analgesic benefits of COX-2 inhibition with the added anti-inflammatory and gastro-protective benefits of 5-LOX inhibition (Source: PubMed PMID: 15128294). These targets are primarily investigated for chronic inflammatory conditions such as osteoarthritis and rheumatoid arthritis. Furthermore, both enzymes are frequently overexpressed in various malignancies, including colon and lung cancer, suggesting that dual inhibition may offer a synergistic approach to cancer chemoprevention and treatment (Source: PubMed PMID: 16461336). Despite their potential, clinical development has faced challenges, including the need to balance systemic safety with the desired multi-pathway blockade.

Other names

Arachidonate 5-lipoxygenase and prostaglandin-endoperoxide synthase 2ALOX5 and PTGS2Dual COX/5-LOX5-LOX/COX-2 dual target

Simultaneous inhibition of 5-lipoxygenase and cyclooxygenase-2 enzymes to block the production of both leukotrienes and prostaglandins from arachidonic acid (Source: PubMed PMID: 15128294).