Lysophospholipids are small,membrane-derived lipids that act through a growing family of G protein-coupled receptors(GPCRs)that account for around 40% of the known lipid GPCRs.They comprise a range of distinct chemica...Lysophospholipids are small,membrane-derived lipids that act through a growing family of G protein-coupled receptors(GPCRs)that account for around 40% of the known lipid GPCRs.They comprise a range of distinct chemical structures and include glycerophospholipids like lysophosphatidic acid(LPA)and sphingoid lipids like sphingosine 1-phosphate(S1P).S1 Phas five cognate GPCRs,four of which mediate the actions of a current medicine used in the treatment of multiple sclerosis(MS):fingolimod(also known as FTY720 or Gilenya),which was approved by the FDA in 2010.Fingolimod has its origins in Chinese medicine as a derivative of fungal natural products.It′s mechanism of action in MS is partly known,through effects on lymphocyte trafficking,however current research has identified direct CNS actions that may represent a particular opportunity area for natural products and their derivatives that can target lysophospholipid receptors.The history of lysophospholipid receptors and fingolimod will be discussed,along with mechanistic aspects of receptor-ligand interactions,particularly those with disease relevance.展开更多
文摘Lysophospholipids are small,membrane-derived lipids that act through a growing family of G protein-coupled receptors(GPCRs)that account for around 40% of the known lipid GPCRs.They comprise a range of distinct chemical structures and include glycerophospholipids like lysophosphatidic acid(LPA)and sphingoid lipids like sphingosine 1-phosphate(S1P).S1 Phas five cognate GPCRs,four of which mediate the actions of a current medicine used in the treatment of multiple sclerosis(MS):fingolimod(also known as FTY720 or Gilenya),which was approved by the FDA in 2010.Fingolimod has its origins in Chinese medicine as a derivative of fungal natural products.It′s mechanism of action in MS is partly known,through effects on lymphocyte trafficking,however current research has identified direct CNS actions that may represent a particular opportunity area for natural products and their derivatives that can target lysophospholipid receptors.The history of lysophospholipid receptors and fingolimod will be discussed,along with mechanistic aspects of receptor-ligand interactions,particularly those with disease relevance.
