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Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein 1: Recent Developments Concerning Substrates and Inhibitors of a Promising Therapeutic Target

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Abstract:

SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.

Keywords: AOC3; Alzheimer's disease; Semicarbazide-sensitive amine oxidase (SSAO); bovine plasma amine oxidase (BPAO); bovine serum amine oxidase (BSAO); diabetes; inhibitors; vascular adhesion protein 1 (VAP-1)

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708785133022

Affiliations: Department of Organic Chemistry, Semmelweis University, Hogyes Endre utca 7, H-1092 Budapest, Hungary.

Publication date: August 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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