A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential.
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.
Lewis
Ian
I
Transplantation Research Department, Novartis Pharma, CH-4002 Basel, Switzerland. ian.lewis@pharma.novartis.com
Bauer
Wilfried
W
Albert
Rainer
R
Chandramouli
Nagarajan
N
Pless
Janos
J
Weckbecker
Gisbert
G
Bruns
Christian
C
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D006224:Cricetinae; D015195:Drug Design; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D013004:Somatostatin; C517782:pasireotide