Abstract
A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy.
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Dogs
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Graft Survival
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Immunosuppressive Agents / chemical synthesis*
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Immunosuppressive Agents / pharmacokinetics
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Immunosuppressive Agents / pharmacology
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Lymphocyte Count
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / pharmacokinetics
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Oxadiazoles / pharmacology
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Radioligand Assay
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Rats
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Rats, Inbred Lew
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Rats, Sprague-Dawley
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Receptors, Lysosphingolipid / agonists*
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Skin Transplantation
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Structure-Activity Relationship
Substances
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Immunosuppressive Agents
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Oxadiazoles
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Receptors, Lysosphingolipid