Somatostatin

Somatostatin structure

Somatostatin

H-1490-GMP, 4006075

What is somatostatin?

Somatostatin is a hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. It is an inhibitor of growth hormone release from the anterior pituitary gland and suppresses the release of a variety of other hormones involved in the regulation of important physiological functions of the gastrointestinal tract. Somatostatin (SST) was isolated and characterized by researchers working in the laboratory of Guillemin at the Salk Institute in 1973.

What does somatostatin look like?

Somatostatin is a cyclic polypeptide containing a disulfide bridge, between Cys-3 and Csy-14 for somatostatin-14 (SST-14) and between Cys-17 and Cys-28 for somatostatin-28 (SST-28). Somatostatin peptides are derived from a precursor protein of 116 amino acids. The precursor is processed into several peptide hormones, including SST-14, SST-28 at the N-terminal, and neuronostatin, which is a 13-residue amidated peptide flanked with the signal peptide.

Somatostatin precursor molecule and location of the disulfide bridges

What role does somatostatin play in the body?

In the body, there exists five somatostatin receptor (SSTR) subtypes, SSTR1 to SSTR5 to which their natural ligands SST-14 and SST-28 bind. SST-14 and SST-28 bind with equal affinity to SSTRs 1–4. However, SST-28 has a 10- to 30-fold higher affinity for SSTR5 than other SSTs, whereas SST-14 has reduced affinity at SSTR5.

Somatostatin mechanism of action

The two somatostatin forms are together considered a global counter regulatory hormone, with inhibitory effects in multiple target tissues. Somatostatin inhibits gastric acid secretion and motility, intestinal absorption, pancreatic bicarbonate and enzyme secretion, and selectively decreases splanchnic and portal blood flow in dogs and humans without affecting mucosal blood flow. Moreover, somatostatin inhibits the secretion of growth hormone (GH), prolactin (PRL), thyrotropin (TSH), cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin, motilin, neurotensin, secretin, glucagon, insulin, and pancreatic polypeptide (PP)2.

SST-14 is the predominant form in the central nervous system and in most peripheral organs, including the gastrointestinal tract, where it can be found in the stomach, duodenum, colon, and pancreas. In contrast, SST-28 is produced mainly by intestinal enteroendocrine cells and represents >50% of the somatostatin content in the small intestine. Furthermore, SST-28 could be used to treat a range of disorders, mostly relating to hormone hypersecretion.

Somatostatin is characterized as a regulatory-inhibitory peptide that can modulate exocrine secretion — for example of gastric acid, intestinal fluid and pancreatic enzymes — as well as endocrine secretion of growth hormone, insulin, glucagon, gastrin, cholecystokinin, vasoactive intestinal peptide (VIP) and secretin. Somatostatin has great potential for the treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. The short half-life of somatostatin however limits its usefulness as an efficient therapeutic modality. Therefore, research has been conducted in the development of new tuned somatostatin derivatives to offer patients a more efficient treatment.

somatostatin receptor

Somatostatin fields of application

Somatostatin is used for various fields of application, such as:

 

  • Ulcer bleeding – Somatostatin plays a crucial role in the management of ulcer bleeding by inhibiting the secretion of various gastrointestinal hormones, including gastrin. This leads to a reduction in gastric acid production, promoting ulcer healing and minimizing the risk of rebleeding.
  • Hemorrhagic gastritis – As a potent inhibitor of gastric acid secretion, somatostatin is employed in the treatment of hemorrhagic gastritis. By suppressing the release of gastrin and other pro-inflammatory peptides, it helps mitigate mucosal damage, contributing to the resolution of gastritis and prevention of further bleeding episodes.
  • Postoperative pancreatic and duodenal fistulae – Somatostatin’s ability to inhibit the secretion of pancreatic enzymes and decrease blood flow to the splanchnic region makes it a valuable therapeutic agent in managing postoperative pancreatic and duodenal fistulae. This helps reduce the volume and enzymatic activity of fistula output, facilitating the healing process.
  • Variceal hemorrhage – In cases of variceal hemorrhage, somatostatin demonstrates its efficacy by lowering portal venous pressure through the constriction of splanchnic blood vessels. This vasoconstrictive effect reduces blood flow to the portal system, subsequently decreasing the risk of bleeding from esophageal varices and providing valuable support in emergency situations.

Who manufactures somatostatin?

Bachem is a leading manufacturer of generic active pharmaceutical ingredients (APIs). We offer a full package for generic APIs to answer your needs: with the regulatory know-how and timely delivery in the right scale for you – from mg to tons. Our commitment is to simplify the complex, making it easier to concentrate on your success.

Strong regulatory affairs support for our generics clients

Bachem has a strong track record in compiling and filing regulatory documents for drug substances in Europe, North America, Japan and China.

We are experienced in writing different types of regulatory dossiers that are adapted to the relevant regional requirements, including:

  • CMC documentation for clinical trial applications
  • Drug master files (DMFs)
  • Dossiers for Certificate of suitability (CEP) application

List of impurities and related  products:

Product numberNameSequence
4033009Somatostatin-14H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4072026([ring-D₅]Phe⁶)-Somatostatin-14H-Ala-Gly-Cys-Lys-Asn-[ring-D₅]Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4025089Somatostatin-14 (reduced)H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4039552Biotinyl-Somatostatin-14Biotinyl-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4027206(D-Phe⁷)-Somatostatin-14H-Ala-Gly-Cys-Lys-Asn-Phe-D-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4031277(D-Trp⁸)-Somatostatin-14H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4013815Tyr-Somatostatin-14H-Tyr-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4019615(Tyr¹¹)-Somatostatin-14H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser-Cys-OH
4013817(Tyr¹)-Somatostatin-14H-Tyr-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4029367Somatostatin-14 (3-14)H-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
4041674Tyr-(D-Dab⁴,Arg⁵,D-Trp⁸)-cyclo-Somatostatin-14 (4-11)H-Tyr-cyclo(-D-Dab-Arg-Phe-Phe-D-Trp-Lys-Thr-Phe)
4025467(D-2-Nal⁵,Cys⁶·¹¹,Tyr⁷,D-Trp⁸,Val¹⁰,2-Nal¹²)-Somatostatin-14 (5-12) amideH-D-2-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-2-Nal-NH₂
4039201(D-Phe⁵,Cys⁶·¹¹,N-Me-D-Trp⁸)-Somatostatin-14 (5-12) amideH-D-Phe-Cys-Phe-N-Me-D-Trp-Lys-Thr-Cys-Thr-NH₂

Somatostatin analogs

Light micrograph of oesophageal cancer

What are somatostatin analogs?

Glucagon-like peptide 1 (GLP-1) at Bachem

Somatostatin analogs provide invaluable therapeutics options

Bachem Regulatory Documentation

CEP

Somatostatin sequence

H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH acetate salt (Disulfide bond)

Somatostatin synonyms

  • Somatostatin-14
  • SRIF
  • SRIF-14
  • Somatotropin Release-Inhibiting Factor
  • Somatostatina
  • Somatostatine

Molecular Information

Molecular Formula

C76H104N18O19S2

Relative Molecular Mass

1637.90 g/mol

CAS-Number

38916-34-6 (net)

Long-term Storage

-20 ± 5°C

In need of a guaranteed, sustained supply of somatostatin API?

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