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Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis.
Arch Pharm Res. 2010 Oct; 33(10):1567-74.AP

Abstract

FTY720 (fingolimod, Novartis) is a promising investigational drug for relapsing forms of multiple sclerosis (MS), an autoimmune and neurodegenerative disorder of the central nervous system. It is currently under FDA review in the United States, and could represent the first approved oral treatment for MS. Extensive, ongoing clinical trials in Phase II/III have supported both the efficacy and safety of FTY720. FTY720 itself is not bioactive, but when phosphorylated (FTY720-P) by sphingosine kinase 2, it becomes active through modulation of 4 of the 5 known G protein-coupled sphingosine 1-phosphate (S1P) receptors. The mechanism of action (MOA) is thought to be immunological, where FTY720 alters lymphocyte trafficking via S1P1. However, MOA for FTY720 in MS may also involve a direct, neurological action within the central nervous system in view of documented S1P receptor-mediated signaling influences in the brain, and this review considers observations that support an emerging neurological MOA.

Authors+Show Affiliations

Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21052934

Citation

Lee, Chang Wook, et al. "Neurological S1P Signaling as an Emerging Mechanism of Action of Oral FTY720 (fingolimod) in Multiple Sclerosis." Archives of Pharmacal Research, vol. 33, no. 10, 2010, pp. 1567-74.
Lee CW, Choi JW, Chun J. Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis. Arch Pharm Res. 2010;33(10):1567-74.
Lee, C. W., Choi, J. W., & Chun, J. (2010). Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis. Archives of Pharmacal Research, 33(10), 1567-74. https://doi.org/10.1007/s12272-010-1008-5
Lee CW, Choi JW, Chun J. Neurological S1P Signaling as an Emerging Mechanism of Action of Oral FTY720 (fingolimod) in Multiple Sclerosis. Arch Pharm Res. 2010;33(10):1567-74. PubMed PMID: 21052934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis. AU - Lee,Chang Wook, AU - Choi,Ji Woong, AU - Chun,Jerold, Y1 - 2010/10/30/ PY - 2010/08/15/received PY - 2010/08/24/accepted PY - 2010/08/23/revised PY - 2010/11/6/entrez PY - 2010/11/6/pubmed PY - 2011/3/8/medline SP - 1567 EP - 74 JF - Archives of pharmacal research JO - Arch. Pharm. Res. VL - 33 IS - 10 N2 - FTY720 (fingolimod, Novartis) is a promising investigational drug for relapsing forms of multiple sclerosis (MS), an autoimmune and neurodegenerative disorder of the central nervous system. It is currently under FDA review in the United States, and could represent the first approved oral treatment for MS. Extensive, ongoing clinical trials in Phase II/III have supported both the efficacy and safety of FTY720. FTY720 itself is not bioactive, but when phosphorylated (FTY720-P) by sphingosine kinase 2, it becomes active through modulation of 4 of the 5 known G protein-coupled sphingosine 1-phosphate (S1P) receptors. The mechanism of action (MOA) is thought to be immunological, where FTY720 alters lymphocyte trafficking via S1P1. However, MOA for FTY720 in MS may also involve a direct, neurological action within the central nervous system in view of documented S1P receptor-mediated signaling influences in the brain, and this review considers observations that support an emerging neurological MOA. SN - 0253-6269 UR - https://www.unboundmedicine.com/medline/citation/21052934/Neurological_S1P_signaling_as_an_emerging_mechanism_of_action_of_oral_FTY720__fingolimod__in_multiple_sclerosis_ L2 - https://dx.doi.org/10.1007/s12272-010-1008-5 DB - PRIME DP - Unbound Medicine ER -