HM74a agonists: will they be the new generation of nicotinic acid?
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.
Martres
Paul
P
Laboratoire GlaxoSmithKline, Centre de Recherches, Les Ulis, France. paul.l.martres@gsk.com
D000818:Animals; D015195:Drug Design; D005483:Flushing / Q000139:chemically induced; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D015394:Molecular Structure; D009525:Niacin / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D011978:Receptors, Nicotinic; D013329:Structure-Activity Relationship
C530636:HCAR2 protein, human; D000960:Hypolipidemic Agents; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin