The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.

Abstract

Nicotinic acid has been used for several decades to treat dyslipidemia. In mice, the lipid-lowing effect of nicotinic acid is mediated by the Gi coupled receptor PUMA-G. In humans, high (GPR109A) and low (GPR109B) affinity nicotinic acid receptors have been characterized. Here we identify monomethylfumarate as a GPR109A agonist. Monomethylfumarate is the active metabolite of the psoriasis drug Fumaderm. We show that monomethylfumarate activates GPR109A in a calcium based aequorin assay, cAMP assay and demonstrate competitive binding with nicotinic acid. We show that GPR109A is highly expressed in neutrophils and epidermal keratinocytes, and that its expression is increased in human psoriatic lesions. Our findings provide evidence that GPR109A is a target for the drug Fumaderm and suggest that niacin should be investigated to treat psoriasis in addition to its role in treating lipid disorders.

• Authors: Hua Tang, Jenny Ying-Lin Lu, Xiaomu Zheng, Yuhua Yang, Jeff D Reagan
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 375 Issue 4 Pg. 562-5 (Oct 31 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18722346 (Publication Type: Journal Article)

Chemical References

• Dermatologic Agents
• Fumarates
• HCAR2 protein, human
• HCAR3 protein, human
• Hypolipidemic Agents
• Maleates
• Receptors, G-Protein-Coupled
• Receptors, Nicotinic
• citraconic acid
• Niacin
• Dimethyl Fumarate

Topics

• Cell Line
• Dermatologic Agents (pharmacology, therapeutic use)
• Dimethyl Fumarate
• Fumarates (pharmacology, therapeutic use)
• Humans
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Maleates (pharmacology, therapeutic use)
• Niacin (pharmacology, therapeutic use)
• Psoriasis (drug therapy)
• Receptors, G-Protein-Coupled (agonists)
• Receptors, Nicotinic