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J Nat Prod. 2011 Apr 25;74(4):900-7. doi: 10.1021/np2000528. Epub 2011 Apr 1.

Fingolimod (FTY720): a recently approved multiple sclerosis drug based on a fungal secondary metabolite.

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  • 1Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, North Carolina 27402-6170, USA.

Abstract

Fingolimod (Gilenya; FTY720), a synthetic compound based on the fungal secondary metabolite myriocin (ISP-I), is a potent immunosuppressant that was approved (September 2010) by the U.S. FDA as a new treatment for multiple sclerosis (MS). Fingolimod was synthesized by the research group of Tetsuro Fujita at Kyoto University in 1992 while investigating structure-activity relationships of derivatives of the fungal metabolite ISP-I, isolated from Isaria sinclairii. Fingolimod becomes active in vivo following phosphorylation by sphingosine kinase 2 to form fingolimod-phosphate, which binds to extracellular G protein-coupled receptors, sphingosine 1-phosphates, and prevents the release of lymphocytes from lymphoid tissue. Fingolimod is orally active, which is unique among current first-line MS therapies, and it has the potential to be used in the treatment of organ transplants and cancer. This review highlights the discovery and development of fingolimod, from an isolated lead natural product, through synthetic analogues, to an approved drug.

PMID:
21456524
[PubMed - indexed for MEDLINE]
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