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      COX inhibitors: a patent review (2011 – 2014)

      Author(s): , ,
      Publication date Created:
      Publication date (Print):
      Journal: Expert Opinion on Therapeutic Patents
      Publisher: Informa Healthcare

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          Abstract

          The COX enzymes play a central role in the biosynthetic pathway of important biological mediators called prostanoids. Differences in regulation of gene expression, stability of transcripts and proteins determine the different biological functions of COX-1 and COX-2. While the COX-1 gene has been considered to be a 'housekeeping' gene expressed in many tissues and cells, COX-2 gene is upregulated during inflammation, hypoxia and in many cancers.

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          Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.

          Kate Shay, Régis Moreau, Eric Smith … (2009)
          Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.
          Article 0 comments Cited 232 times – based on 0 reviews     Review now
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            Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2.

            Patricia McGettigan, David Henry (2006)
            Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older nonselective NSAIDs. To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors. Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies. Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs. Two people independently extracted data and assessed study quality with disagreements resolved by consensus. Data were combined using a random-effects model. A dose-related risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18). This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.
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              Recent developments in nitric oxide donor drugs.

              Daniel G. Miller, I L Megson (2007)
              During the 1980s, the free radical, nitric oxide (NO), was discovered to be a crucial signalling molecule, with wide-ranging functions in the cardiovascular, nervous and immune systems. Aside from providing a credible explanation for the actions of organic nitrates and sodium nitroprusside that have long been used in the treatment of angina and hypertensive crises respectively, the discovery generated great hopes for new NO-based treatments for a wide variety of ailments. Decades later, however, we are still awaiting novel licensed agents in this arena, despite an enormous research effort to this end. This review explores some of the most promising recent advances in NO donor drug development and addresses the challenges associated with NO as a therapeutic agent.
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                Author and article information

                Journal
                Title: Expert Opinion on Therapeutic Patents
                Abbreviated Title: Expert Opinion on Therapeutic Patents
                Publisher: Informa Healthcare
                ISSN (Print): 1354-3776
                ISSN (Electronic): 1744-7674
                Publication date Created: September 15 2015
                Publication date (Print): November 13 2015
                Volume: 25
                Issue: 12
                Pages: 1357-1371
                Article
                DOI: 10.1517/13543776.2015.1090973
                PubMed ID: 26566186
                SO-VID: 2a1f841f-fadd-4abf-b194-17d7c716eca3
                Copyright © © 2015
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