SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile
Abstract
Objective The aim of the present study was to identify a small, metabolically stable somatotropin release inhibiting factor (SRIF) analog with a more universal binding profile similar to that of natural somatostatin, resulting in improved pharmacological properties and hence new therapeutic uses. Design A rational drug design approach was followed by synthesizing alanine-substituted SRIF-14 analogs to determine the importance of single amino acids in SRIF-14 for SRIF receptor subtype binding. The incorporation of structural elements of SRIF-14 in a stable cyclohexapeptide template in the form of modified unnatural amino acids resulted in the identification of the novel cyclohexapeptide SOM230. Results SOM230 binds with high affinity to SRIF receptor subtypes sst1, sst2, sst3 and sst5 and displays a 30- to 40-fold higher affinity for sst1 and sst5 than Sandostatin (octreotide; SMS 201-995) or Somatuline (BIM 23014). In vitro, SOM230 effectively inhibited the growth hormone releasing hormone (GHRH)-induced growth hormone (GH) release in primary cultures of rat pituitary cells with an IC(50) of 0.4+/-0.1 nmol/l (n=5). In vivo, SOM230 also potently suppressed GH secretion in rats. The ED(50) values determined at 1 h and 6 h post injection of SOM230 indicated its very long duration of action in vivo. This property was also reflected in pharmacokinetic studies comparing plasma levels of SMS 201-995 and SOM230 after subcutaneous application. Whereas SMS 201-995 had a terminal elimin…
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Pasireotide is a multireceptor-targeted somatostatin analogue with high affinity for 4 of the 5 somatostatin receptor subtypes, including sst2 and sst5.
“Pasireotide is a multireceptor-targeted somatostatin analogue with high affinity for 4 of the 5 somatostatin receptor subtypes, including sst2 and sst5.”
From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [98]
The affinity of pasireotide for sst5 is higher than that of octreotide.
“The affinity of pasireotide for sst5 is higher than that of octreotide (98,99).”
From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [98]
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- Authors
- Bruns, C., Lewis, I., Briner, U., Meno-Tetang, G., & Weckbecker, G.
- Affiliations
- Novartis (Switzerland) (CH)
- Corresponding author
- Bruns, C
- Weckbecker, G
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-05-01
- Volume
- 146
- Issue
- 5
- Pages
- 707-716
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2168906621
- Cited by
- 692
- References
- 0
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 26 · 2023: 9 · 2022: 19 · 2021: 30 · 2020: 30 · 2019: 19 · 2018: 35 · 2017: 24 · 2016: 48 · 2015: 44 · 2014: 38 · 2013: 42 · 2012: 36
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- pasireotide, somatostatin analogues, sst1, sst5, cyclohexapeptides, octreotide, growth hormone secretion, insulin-like growth factor I, antisecretory effect, pharmacokinetics, duration of action, pituitary cells
- MeSH terms
- Animals, Binding, Competitive, Dose-Response Relationship, Drug, Glucagon, Humans, Insulin Antagonists, Insulin-Like Growth Factor I, Male, Rats, Inbred Lew, Somatostatin, Receptors, Somatostatin, Human Growth Hormone, Protein Isoforms, Rats
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