Abstract
A rational drug design approach, capitalizing on structure-activity relationships and involving transposition of functional groups from somatotropin release inhibitory factor (SRIF) into a reduced size cyclohexapeptide template, has led to the discovery of SOM230 (25), a novel, stable cyclohexapeptide somatostatin mimic that exhibits unique high-affinity binding to human somatostatin receptors (subtypes sst1-sst5). SOM230 has potent, long-lasting inhibitory effects on growth hormone and insulin-like growth factor-1 release and is a promising development candidate currently under evaluation in phase I clinical trials.
MeSH terms
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Animals
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CHO Cells
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COS Cells
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Cricetinae
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Drug Design
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Humans
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Ligands
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Magnetic Resonance Spectroscopy
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Molecular Mimicry
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology
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Radioligand Assay
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Receptors, Somatostatin / metabolism*
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Somatostatin / analogs & derivatives
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Somatostatin / chemical synthesis*
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Somatostatin / chemistry*
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Somatostatin / pharmacology
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Structure-Activity Relationship
Substances
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Ligands
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Oligopeptides
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Peptides, Cyclic
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Receptors, Somatostatin
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Somatostatin
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pasireotide