Drug discovery in the metabolic syndrome: context and some recent developments

Abstract

The metabolic syndrome, encompassing the clinically distinct but related areas of dyslipidaemia, insulin resistance, obesity and vascular disease, offers a wide arena for drug discovery. There is substantial and growing unmet medical need, particularly as the worldwide epidemic of obesity continues to develop. There are also many targets and biological mechanisms that can be exploited. However, the context for clinical development is challenging because of the many ways in which the syndrome can be approached. As with most therapeutic areas, preclinical data provide only limited confidence in the potential of a novel target in humans. In this review, the author outlines the context for drug discovery in the metabolic syndrome, the clinical and biological scope and recent developments in preclinical models. Finally, existing examples of drug targets for a range of biological mechanisms are considered, outlining their biology and points relevant to lead identification and optimisation and clinical development.

Keywords::

• 11β-hydroxysteroid dehydrogenase
• AMP-activated protein kinase
• animal model
• atherosclerosis
• dyslipidaemia
• insulin resistance
• nuclear hormone receptor
• obesity