原创力文档sphingosine 1-phosphate receptor 1 as a useful target for treatment of multiple sclerosis鞘氨醇1-phosphate受体1作为一个有用的治疗多发性硬化症的目标.pdfVIP
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sphingosine 1-phosphate receptor 1 as a useful target for treatment of multiple sclerosis鞘氨醇1-phosphate受体1作为一个有用的治疗多发性硬化症的目标
Pharmaceuticals 2012, 5, 514-528; doi:10.3390/ph5050514
OPEN ACCESS
Pharmaceuticals
ISSN 1424-8247
/journal/pharmaceuticals
Review
Sphingosine 1-Phosphate Receptor 1 as a Useful Target for
Treatment of Multiple Sclerosis
Kenji Chiba * and Kunitomo Adachi
Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku,
Yokohama, Kanagawa 227-0033, Japan; E-Mail: Adachi.Kunitomo@mc.mt-pharma.co.jp (K.A.)
* Author to whom correspondence should be addressed; E-Mail: Chiba.Kenji@mk.mt-pharma.co.jp;
Tel.: +81-45-963-4342; Fax: +81-45-963-7316.
Received: 5 April 2012; in revised form: 24 April 2012 / Accepted: 15 May 2012 /
Published: 18 May 2012
Abstract: Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, is generated from
sphingosine by sphingosine kinases and binds five known cell surface receptors. S1P
receptor 1 (S1P ) plays an essential role in lymphocyte egress from secondary lymphoid
1
organs (SLO), as evinced by the inability of lymphocytes to exit from the SLO in mice
lacking lymphocytic S1P . Fingolimod hydrochloride (FTY720) is a first-in-class, orally
1
active, S1P receptor modulator with a structure closely related to sphingosine. FTY720 was
first synthesized by chemical modification of a natural product, myriocin. FTY720 is
effectively converted to an active metabolite, FTY720 phosphate (FTY720-P) by
sphingosine ki
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