HM74a agonists: will they be the new generation of nicotinic acid?

Curr Top Med Chem. 2009;9(5):428-35. doi: 10.2174/156802609788340814.


The discovery of HM74a as a high affinity receptor for nicotinic acid has opened up new areas for investigation. Since its discovery, several new chemical entities have been reported as HM74a agonists. One of them, MK-0354, has been tested in phase II studies, but despite significant decreases in Free Fatty Acid levels with absence of flushing events in clinical studies, it failed to demonstrate effects on LDL-Cholesterol, Triglycerides and HDL-Cholesterol. These surprising results lead to questions about the reality of HM74a as the unique receptor responsible for the lipid modulating effects of nicotinic acid. This review summarizes these recent developments, and the novel HM74a antagonist structures recently published.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Flushing / chemically induced
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacokinetics
  • Hypolipidemic Agents / therapeutic use
  • Molecular Structure
  • Niacin* / adverse effects
  • Niacin* / chemistry
  • Niacin* / pharmacokinetics
  • Niacin* / therapeutic use
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, Nicotinic
  • Structure-Activity Relationship


  • HCAR2 protein, human
  • Hypolipidemic Agents
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Niacin