Recent progress in the discovery of niacin receptor agonists.

Niacin (nicotinic acid) favorably affects multiple serum lipid parameters that are believed to be cardiovascular risk factors, but is also associated with a cutaneous flushing adverse effect. The recent discovery of a G-protein-coupled receptor target for niacin (termed GPR109alpha) has stimulated interest in the discovery of new compounds with niacin-like effects on lipids, but with fewer adverse effects. This review discusses the progress made toward the discovery of such molecules and highlights the pharmacological models used to enable their identification. The advances made in both these areas may help to determine whether GPR109alpha is the molecular target responsible for the beneficial anti-atherogenic effects of niacin.