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The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.
Biochem Biophys Res Commun. 2008 Oct 31; 375(4):562-5.BB

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+Show Affiliations

Department of Metabolic Disorders, Amgen San Francisco, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18722346

Citation

Tang, Hua, et al. "The Psoriasis Drug Monomethylfumarate Is a Potent Nicotinic Acid Receptor Agonist." Biochemical and Biophysical Research Communications, vol. 375, no. 4, 2008, pp. 562-5.
Tang H, Lu JY, Zheng X, et al. The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochem Biophys Res Commun. 2008;375(4):562-5.
Tang, H., Lu, J. Y., Zheng, X., Yang, Y., & Reagan, J. D. (2008). The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochemical and Biophysical Research Communications, 375(4), 562-5. https://doi.org/10.1016/j.bbrc.2008.08.041
Tang H, et al. The Psoriasis Drug Monomethylfumarate Is a Potent Nicotinic Acid Receptor Agonist. Biochem Biophys Res Commun. 2008 Oct 31;375(4):562-5. PubMed PMID: 18722346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. AU - Tang,Hua, AU - Lu,Jenny Ying-Lin, AU - Zheng,Xiaomu, AU - Yang,Yuhua, AU - Reagan,Jeff D, Y1 - 2008/08/21/ PY - 2008/08/07/received PY - 2008/08/09/accepted PY - 2008/8/30/pubmed PY - 2008/10/28/medline PY - 2008/8/30/entrez SP - 562 EP - 5 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 375 IS - 4 N2 - 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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/18722346/The_psoriasis_drug_monomethylfumarate_is_a_potent_nicotinic_acid_receptor_agonist_ DB - PRIME DP - Unbound Medicine ER -