Abstract
KRN7000, an anticancer drug candidate developed by Kirin Brewery Co. in 1995, is an α-galactosyl ceramide. It is a ligand making a complex with CD1d protein, and it stimulates invariant natural killer T (NKT) cells, which are one of the lineages of immunocytes. NKT cells activated by recognition of the CD1d/KRN7000 complex with its invariant T-cell receptor (TCR) can induce both protective and regulatory immune responses. To determine the recognition and activation mechanisms of NKT cells and to develop drug candidates more effective than KRN7000, a large number of analogs of KRN7000 have been synthesized. Some of them show potent bioactivities and have the potential of being utilized as therapeutic agents. In this review, structure-activity relationship studies of novel glycolipids which stimulate NKT cells efficiently are summarized.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antigens, CD1d / immunology
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Antigens, CD1d / metabolism
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Cytokines / biosynthesis
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Cytokines / immunology
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Galactosylceramides / chemical synthesis*
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Galactosylceramides / pharmacology
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Galactosylceramides / therapeutic use
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Glycosphingolipids / chemical synthesis*
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Glycosphingolipids / pharmacology
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Glycosphingolipids / therapeutic use
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Humans
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Lymphocyte Activation / drug effects
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Mice
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Natural Killer T-Cells / drug effects*
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Natural Killer T-Cells / immunology
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Neoplasms / drug therapy*
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Neoplasms / immunology
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Structure-Activity Relationship
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Th1-Th2 Balance / drug effects
Substances
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Antigens, CD1d
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Antineoplastic Agents
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CD1D protein, human
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Cytokines
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Galactosylceramides
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Glycosphingolipids
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Receptors, Antigen, T-Cell
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KRN 7000