Abstract:
:Sphingosine 1-phosphate (S1P) evokes a plethora of physiological responses by stimulating members of a G protein-coupled receptor family, known as S1P receptors. Currently five different mammalian S1P receptor subtypes, S1P₁₋₅, each with a different cellular expression pattern, were identified. The S1P₁ receptor in particular has attracted major interest throughout the pharmaceutical industry following the breakthrough discovery that this S1P receptor subtype is critically involved in the regulation of lymphocyte trafficking through secondary lymphoid organs. Since then, examples of synthetic S1P₁ agonists with lymphocyte reducing and immunomodulating activity demonstrated efficacy in numerous preclinical models of autoimmune disease and transplantation. Notably FTY720 (fingolimod), a pro-drug that is phosphorylated in vivo and converted into a non-selective S1P₁,₃,₄,₅ receptor agonist, has been widely used to increase the understanding of S1P₁ receptor biology. Results from recently completed phase III clinical trials using FTY720 paved the way for this non-selective S1P₁ receptor agonist to become the first oral therapy in multiple sclerosis, with potential expansion into many other autoimmune diseases. This review briefly outlines the field of S1P₁ receptor biology and summarizes recent approaches in medicinal chemistry to discover potent and selective S1P₁ receptor agonists. In particular, the complexity of discovering a molecule akin to FTY720 but with an improved side-effect profile will be discussed.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Bolli MH,Lescop C,Nayler Odoi
10.2174/1568026611109060726subject
Has Abstractpub_date
2011-01-01 00:00:00pages
726-57issue
6eissn
1568-0266issn
1873-4294pii
BSP/CTMC/E-Pub/-00049-11-7journal_volume
11pub_type
杂志文章,评审abstract::Results of various projects on Mexican Indian ethnobotany and some of the subsequent pharmacological and phytochemical studies are summarised focusing both on chemical-pharmacological as well as anthropological (ethnopharmacological) aspects of our research. We have identified taste and smell properties of medicinal (...
journal_title:Current topics in medicinal chemistry
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doi:10.2174/1568026033392570
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abstract:: ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
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更新日期:2020-12-11 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 社论
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更新日期:2015-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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更新日期:2011-01-01 00:00:00
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更新日期:2017-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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更新日期:2016-01-01 00:00:00
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更新日期:2012-01-01 00:00:00
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更新日期:2014-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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更新日期:2016-01-01 00:00:00
abstract::There are currently (July, 2002) six protease inhibitors approved for the treatment of HIV infection, each of which can be classified as peptidomimetic in structure. These agents, when used in combination with other antiretroviral agents, produce a sustained decrease in viral load, often to levels below the limits of ...
journal_title:Current topics in medicinal chemistry
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更新日期:2004-01-01 00:00:00