Abstract
Introduction of polar groups in a series of potent CCR5 antagonists which are very likely to adversely affect the conduction system in the heart led to the identification of NIBR-1282 which did not show adverse effects when tested in an isolated rabbit heart ex vivo model. Administration of NIBR-1282 in combination with a non-efficacious dose of CsA led to significant prolongation of kidney allograft survival in cynomolgus monkeys.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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CCR5 Receptor Antagonists*
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CHO Cells / drug effects
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Caco-2 Cells / drug effects
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Chemokine CCL3 / metabolism
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Cricetinae
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Cricetulus
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Cyclosporine / pharmacology
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Cytochrome P-450 Enzyme Inhibitors
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Dogs
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Ether-A-Go-Go Potassium Channels / metabolism
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Graft Survival
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Heart / drug effects*
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Humans
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Immunosuppressive Agents / pharmacology
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Kidney Transplantation
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Macaca fascicularis
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Pyridines / chemical synthesis
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Pyridines / pharmacokinetics
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Pyridines / pharmacology*
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Rabbits
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Radioligand Assay
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Rats
Substances
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CCL3 protein, human
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CCR5 Receptor Antagonists
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Chemokine CCL3
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Cytochrome P-450 Enzyme Inhibitors
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Ether-A-Go-Go Potassium Channels
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Immunosuppressive Agents
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KCNH1 protein, human
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NIBR-1282
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Pyridines
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Cyclosporine