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Biochem Biophys Res Commun. 2008 Oct 31;375(4):562-5. doi: 10.1016/j.bbrc.2008.08.041. Epub 2008 Aug 21.

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

Author information

1
Department of Metabolic Disorders, Amgen San Francisco, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.

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.

PMID:
18722346
DOI:
10.1016/j.bbrc.2008.08.041
[Indexed for MEDLINE]

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