From Natural Product to the First Oral Treatment for Multiple Sclerosis: The Discovery of FTY720 (Gilenya™)?

• Published in: Current opinion in chemical biology Vol. 32; pp. 60 - 66
• Main Author: Zécri, Frédéric J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2016
• Subjects: Administration, Oral; Animals; Biological Products - administration & dosage; Biological Products - therapeutic use; Fingolimod Hydrochloride - therapeutic use; Humans; Multiple Sclerosis - drug therapy
• ISSN: 1367-5931; 1879-0402
• DOI: 10.1016/j.cbpa.2016.04.014

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•Derivatization of natural product Myriocin led to the discovery of FTY720.•FTY720 is a strong immune-modulator with a unique mode of action.•Target elucidation revealed the role of S1P1 in lymphocyte trafficking.•First oral treatment approved for relapsing-remitting multiple sclerosis.
Multiple sclerosis is a devastating chronic autoimmune disease affecting women and men of all ages. Inflammation of the central nervous system causes demyelination and ultimately neuropsychological dysfunction. Myriocin, a natural product with strong immunosuppressant activity was interrogated leading to a new class of immunomodulator with a unique mode of action. In this review, we will summarize these findings, the mechanism hypothesis and discuss the data's ultimately leading to the approval of Gilenya™ as the first oral treatment for multiple sclerosis.