What is Somatostatin?

Somatostatin is a peptide hormone that plays a crucial role in regulating various physiological functions in the body. It is a polypeptide hormone produced by delta cells , which can be found in the pancreas and the hypothalamus of the brain.


  • Inhibition of hormone secretion
    Somatostatin acts as an inhibitor of the release of various hormones. By inhibiting the release of these hormones, somatostatin helps to maintain hormonal balance in the body.

  • Regulation of gastrointestinal function
    In the digestive system, somatostatin regulates the secretion of gastric acid, pancreatic enzymes, and bile. It also inhibits the absorption of nutrients from the intestine.

  • Modulation of Neurotransmission
    It is involved in various brain functions, including cognition, memory, and mood regulation.

  • Inhibition of Cell Growth: Somatostatin has been shown to inhibit cell proliferation and growth in various tissues, including tumors.


Somatostatin-14 and -28

The peptide hormone somatostatin was first discovered in hypothalamic extracts and identified as an inhibitor of the secretion of growth hormone secretion. Somatostatin is also called somatotropin release-inhibiting factor (SRIF). Its name is derived from this activity. Subsequently, somatostatin was shown to be an essential regulatory hormone of the gastrointestinal tract. It also acts as a modulator of neurotransmission in the CNS and affects cell proliferation. Somatostatin inhibits the release of various hormones such as growth hormone, TSH, glucagon, VIP, insulin, CCK, and gastrin.

Somatostatin is produced by the δ-cells of the pancreas and, to a lesser extent, in the hypothalamus and by paracrine cells in the gastrointestinal tract. Somatostatin exists in two active isoforms:

Somatostatin-14 (SRIF-14)


Somatostatin-28 (SRIF-28)




Signal peptide                                           Propeptide (bold: neuronostatin-19)



Both SRIF isoforms contain a disulfide bridge. Somatostatin-14 and -28 are produced by alternate cleavage of preprosomatostatin. Additionally, the 116 amino acid protein is the precursor of the neurohormones neuronostatin-13 and -19.

The relative amount of the somatostatin variants depends on the type of tissue releasing them. SRIF-14 is secreted especially in the nervous system and by pancreatic δ-cells, whereas intestinal cells predominantly produce the larger peptide. Somatostatin-14 and -28 may also differ in activity. Whereas SRIF-28 more efficiently inhibits the release of growth hormone, SRIF-14 is more potent in inhibiting secretion of glucagon.

Both SRIF isoforms contain a disulfide bridge. Somatostatin-14 and -28 are produced by alternate cleavage of preprosomatostatin. Additionally, the 116 amino acid protein is the precursor of the neurohormones neuronostatin-13 and -19.

The relative amount of the somatostatin variants depends on the type of tissue releasing them. SRIF-14 is secreted especially in the nervous system and by pancreatic δ-cells, whereas intestinal cells predominantly produce the larger peptide. Somatostatin-14 and -28 may also differ in activity. Whereas SRIF-28 more efficiently inhibits the release of growth hormone, SRIF-14 is more potent in inhibiting secretion of glucagon.

Somatostatin receptors

Somatostatin triggers numerous physiological processes by binding to G-protein-coupled receptors located on the surface of various cell types. Five somatostatin receptor subtypes are known, SST1 –SST5, to which the hormone (both isoforms) binds with equally high affinity. The cyclic structure and the FWKT motif of the ring are essential for receptor binding. The somatostatin-related neuropeptides cortistatin-17 and -29 are further endogenous ligands for the five receptors.

Somatostatin-14              AGCKNFFWKTFTSC

Cortistatin-17              DRMPCRNFFWKTFSSCK

Octreotate                                fCYwKTCT     

Though all of them inhibit adenyl cyclase, the five somatostatin receptor subtypes activate different signaling mechanisms in the cell.

Somatostatin analogs as (D-Trp8)-somatostatin-14 are more resistant to enzymatic degradation and show different abilities to inhibit the production of growth hormone, insulin or glucagon.


Use of somatostatin and analogs as drugs

In addition to the downregulation of gastrointestinal hormones, somatostatin inhibits the production of pancreatic and gastric enzymes. For this reason it has been employed in the treatment of gastrointestinal disorders such as bleeding peptic ulcers and gallbladder fistulae. As the hormone has a half-life of merely 1-3 minutes, stable analogs such as octreotide (with a half-life of ca. 100 min in plasma) and vapreotide have been developed for treating these conditions.

Somatostatin agonists could be tools in the management of obesity, as SRIF counteracts the expression of hormones involved in the uptake of nutrients including the orexigenic hormone ghrelin. Octreotide has been evaluated for the treatment of hypothalamic obesity, a condition caused by insulin hypersecretion.

The somatostatin analogs octreotide and lanreotide are approved drugs for treating acromegaly, a disorder resulting from excessive production of growth hormone. In most cases, GH hypersecretion is caused by a benign pituitary tumor.     

Somatostatin is involved in the proliferation of both normal and tumorigenic cells. As somatostatin receptors are overexpressed in various types of tumors, the hormone became a target in cancer research and a lead for developing receptor-specific agonists. These compounds found use in cancer therapy.

Most tumors carrying somatostatin receptors may express multiple subtypes. Amongst them, SST2 is predominantly expressed. The somatostatin agonists octreotide, lanreotide and vapreotide preferably bind to SST2.

Due to the high affinity and specificity of the compounds for SST2 they were modified by attaching chelators enabling them to transport radionuclides to the target cancerous growth. Edotreotide (DOTATOC, DOTA-(Tyr)-octreotide), the even more SST2-specific DOTATOC analog DOTATATE (DOTA-(Tyr)-octreotate), pentetreotide (DTPA-octreotide, “octreoscan”) and DOTALAN (DOTA-Lanreotide) have found use as radiodiagnostics and imaging agents or as radiotherapeutics, e.g., for the treatment of neuroendrocrine tumors such as somatotropin- and thyrotropin-secreting pituitary adenomas and carcinoids. Macrocycles as DOTA form extraordinarily stable chelates with radioisotopes such as 68Ga, 111In, 90Y, or 177Lu and carry them to malignant tissue to be located or destroyed by radiation whilst keeping damage to healthy tissue low. The radionuclide has to be generated and complexed by the peptide immediately before use.




Multiconformational NMR analysis of sandostatin (octreotide): equilibrium between beta-sheet and partially helical structures. Melacini, G., Zhu, Q., Goodman, M. (1997) Biochemistry 36: 1233-1241



Pasireotide, a somatostatin agonist approved for the treatment of Cushing’s disease, preferably binds to SST5. The cyclopeptide inhibits corticotropin secretion and thus reduces cortisol levels.





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For decades, somatostatin-related drugs have been of interest in the areas of endocrinology and oncology. Somatostatin was initially viewed as an attractive candidate for the treatment of cancer due to its ability to block hormone release and cell growth after binding to its receptors; however, the native somatostatin peptide exhibited disadvantages such as a short half-life and rebound hypersecretion upon discontinuation. To overcome these obstacles, somatostatin analogs (SSAs) were designed with longer half-lives and improved pharmacologic efficacy and have continued to be a focus of drug development (1). Octreotide (Sandostatin®), the first SSA to be developed was approved by the U.S. Food and Drug Administration (FDA) in 1988. More recently, lanreotide (Somatuline®) was approved for the treatment of acromegaly in 2007 and for the treatment of neuroendocrine tumors in 2014. Pasireotide (Signifor®) was approved for the treatment of Cushing’s disease in2012. There are several somatostatin-related drugs currently in various phases of clinical development as shown in Table 1.

Product NameActive IngredientCondition TreatedHighest PhaseCompany NameMechanism of Action (MOA)
Octreotide Depot MARoctreotideDiarrhea(I)Phase IGP PharmSomatostatin Receptor 2 (SSTR2) Agonist
PT201octreotideAcromegaly(I), Carcinoid Tumors(I)Phase IPeptron Inc, AZAD Pharma AGSomatostatin Receptor 2 (SSTR2) Agonist
Tozariderhenium-188 somatostatin analogrhenium-188 somatostatin analogPhase IBayer Ag,
Andarix Pharmaceuticals, Diatide Inc,
Xanthus Pharmaceuticals, Inc.,
Schering AG,
Bryan Oncor
Somatostatin Receptor (SSTR) Agonist
CAM2029octreotide chlorideAcromegaly(II), Neuroendocrine Tumor(II), Carcinoid Tumors(I)Phase IICamurus AB, Novartis AGSomatostatin Receptor 2 (SSTR2) Agonist
COR005somatoprimAcromegaly(II), Carcinoid Tumors(I), Cushing's Syndrome(I), Diabetic Retinopathy(I)Phase IIDeveloGen AG, Aspireo Pharmaceuticals Limited, Strongbridge Biopharma PlcSomatostatin Receptor 2 (SSTR2) Agonist, Somatostatin Receptor 4 (SSTR4) Agonist, Somatostatin Receptor 5 (SSTR5) Agonist
TF2984--Acromegaly(II)Phase IIItalfarmaco SpASomatostatin Receptor (SSTR) Agonist
Octreotide SDIoctreotide acetateAcromegaly(II), Neuroendocrine Tumor(II)Phase IIGlide Pharmaceutical Technologies Limited, Albany Molecular Research Inc., Paladin Labs Inc.Somatostatin Receptor 2 (SSTR2) Agonist
SomaDEX--Hormone Refractory Metastatic Prostate Cancer(II), Solid Tumors(I)Phase IIDexTech Medical ABSomatostatin Receptor (SSTR) Agonist
Lutatheralutetium Lu 177 dotatateNeuroendocrine Tumor(PA)Pending ApprovalBioSynthema Inc (Originator, Developer),

Advanced Accelerator Applications SA (Co-Developer),

FUJIFILM RI Pharma Co Ltd (Distributor, Sales/Marketing),

Covidien (Sales/Marketing)
Not Applicable
Mycapssaoctreotide acetateAcromegaly(PA),


Neuroendocrine Tumor®
Pending ApprovalChiasma Inc  (Primary Owner, Developer)Somatostatin Receptor 2 (SSTR2) Agonist

Table 1: Somatostatin-Related Drugs in Clinical Development (2)


Phase I Candidates

GP Pharm is developing a controlled release depot formulation of octreotide. Octreotide Depot MAR is polymer matrix micro-encapsulated and this formulation is being developed as a one week treatment of chemo-therapy induced diarrhea. It has finished pre-clinical development. GP Pharm is seeking a partner for co-development or divestment of the project (3).

Peptron is developing a generic version of Sandostatin LAR® known as PT201. This product contains octreotide as the active ingredient and is being developed for the treatment of acromegaly and carcinoid tumors. In collaboration with AZAD Pharma, Peptron has completed a pilot bioequivalence study in healthy volunteers (2).

Tozaride is a cancer therapy being developed by Andarix Pharmaceuticals. The product is a high affinity somatostatin analog labeled withthe radioisotope rhenium-188, which specifically targets tumors over expressing somatostatin receptors. A phase I trial has been completed for Tozaride for the treatment of advanced lung cancer. In addition, Tozaride has been granted orphan drug designation by the FDA for the treatment of small cell lung cancer (2).

Phase II Candidates

Novartis and Camurus are developing CAM2029, a long-acting octreotide FluidCrystal® formulation. The product is being developed as an alternative to existing long-acting somatostatin analog formulations for the treatment of acromegaly, neuroendocrine tumors and other indications. CAM2029 is designed as a ready-to-use injection for self-administration. In 2016, Camurus completed a Phase II study of CAM2029 in patients with acromegaly and neuroendocrine tumors. Phase III trials are expected to commence in 2017 (4).

Strongbridge Biopharma is developing COR005 or somatoprim, a novel somatostatin analog for the treatment of acromegaly, Cushing’s disease, neuroendocrine tumors and diabetic retinopathy. The initial indication for somatoprim is acromegaly and Phase II clinical trials are underway. In 2015, Stongbridge Biopharma reported that it received orphan designation for COR005 from both the European Medicines Agency (EMA) and the FDA (2).

Italfarmaco is developing ITF2984, a somatostatin analog, for the treatment of acromegaly and cancer. In 2016, Italfarmaco completed a Phase II trial of ITF2984 for the treatment of acromegaly (2).

Glide Technologies is developing Octreotide SDI®, a solid dose formulation of octreotide acetate, for the treatment of acromegaly and neuroendocrine tumors. The product is delivered via Glide’s needle-free solid dose injection system (SDI). In 2016, Glide Technologies reported results from a clinical proof-of-concept study that showed Octreotide SDI achieved bioequivalence to Sandostatin®, the currently marketed immediate release liquid injectable product (2).

SomaDex is a stabilized form of somatostatin with an extended-half life that is being developed by DexTech AB. The product consists of somatostatin coupled to a modified hydroxypolymer conjugate. A clinical phase II/pilot study was conducted between 2006 and 2009 on castration resistant prostate cancer patients with results showing a good symptom relieving effect regarding skeletal related pain (5).

Pending Approval

Advanced Accelerator Applications is developing Lutathera®, a Lu-177-labeled somatostatin analog for the treatment of gastroenteropancreatic neuroendocrine tumors. Lutathera has received orphan drug designation from both the EMA and the FDA. In 2016, the company submitted a New Drug Application (NDA) to the FDA and Priority Review was granted for Lutathera. The company also submitted a Marketing Authorization Application (MAA) to the EMA and Accelerated Assessment was granted for Lutathera; however, the review period was recently modified to a standard review period (1).

In 2015, Chiasma completed a Phase III trial of Mycapssa®, the company’s oral formulation of octreotide, in acromegaly and later submitted an NDA to the FDA. In 2016, the FDA completed their review of Chiasma’s NDA for Mycapssa and indicated that the NDA is not ready for approval in its present form. The company is conducting an additional Phase III trial in acromegaly to support a potential MAA with the EMA (1).


Somatostatin analogs hold promise for the treatment of cancers, acromegaly and other conditions. To support companies and organizations developing somatostatin-related drugs, Bachem offers generic API such as octreotide, lanreotide, pasireotide, somatostatin and the production of peptide-based new chemical entities. In addition, Bachem offers a selection of over 30 somatostatin peptides and analogs for research at shop.bachem.com.



(1)  E. Wolin, The expanding role of somatostatin analogs in the management of neuroendocrine tumors, Gastrointest Cancer Res. 5, 161-168 (2012)

(2)  Medtrack (2016)

(3)  Products, GP Pharm (2016)

(4)  Camurus announces completion of Phase 2 study of CAM2029 in patients with acromegaly and neuroendocrine tumors, Nasdaq GlobeNewswire. July 12 (2016)

(5) SomaDex, DexTech (2016)