Lanreotide

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Lanreotide
Lanreotide.svg
Clinical data
Trade names Somatuline
Other namesLanreotide acetate (JAN JP), Lanreotide acetate (USAN US)
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:C
Routes of
administration 		Intramuscular, subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Approximately 80%
Protein binding 78%
Metabolism In GI tract
Elimination half-life 2 hours (immediate release)
5 days (sustained release)
Excretion Mostly bile duct
Identifiers
  • 3-(2-naphthyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide (2->7)-disulfide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.215.992 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C54H69N11O10S2
Molar mass 1096.33 g·mol−1
3D model (JSmol)
  • C[C@H]([C@@H](C(=O)N)NC(=O)[C@@H]1CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)C(C)C)CCCCN)Cc2c[nH]c3c2cccc3)Cc4ccc(cc4)O)NC(=O)[C@@H](Cc5ccc6ccccc6c5)N)O
  • InChI=1S/C54H69N11O10S2/c1-29(2)45-54(75)63-44(53(74)65-46(30(3)66)47(57)68)28-77-76-27-43(62-48(69)38(56)23-32-15-18-33-10-4-5-11-34(33)22-32)52(73)60-41(24-31-16-19-36(67)20-17-31)50(71)61-42(25-35-26-58-39-13-7-6-12-37(35)39)51(72)59-40(49(70)64-45)14-8-9-21-55/h4-7,10-13,15-20,22,26,29-30,38,40-46,58,66-67H,8-9,14,21,23-25,27-28,55-56H2,1-3H3,(H2,57,68)(H,59,72)(H,60,73)(H,61,71)(H,62,69)(H,63,75)(H,64,70)(H,65,74)/t30-,38-,40+,41+,42-,43+,44+,45+,46+/m1/s1 X mark.svgN
  • Key:PUDHBTGHUJUUFI-SCTWWAJVSA-N X mark.svgN
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Lanreotide, sold under the brand name Somatuline among others, is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analogue of somatostatin, like octreotide.

Contents

Lanreotide (as lanreotide acetate) is manufactured by Ipsen. It is available in several countries, including the United Kingdom, Australia and Canada, and was approved for sale in the United States by the Food and Drug Administration (FDA) on August 30, 2007. [2]

Medical uses

Lanreotide is used in the treatment of acromegaly, due to both pituitary and non-pituitary growth hormone-secreting tumors, and the management of symptoms caused by neuroendocrine tumors, particularly carcinoid tumors and VIPomas. In the United States and Canada, lanreotide is only indicated for the treatment of acromegaly. In the United Kingdom, it is also indicated in the treatment of thyrotrophic adenoma, [3] a rare tumor of the pituitary gland which secretes TSH.

Lanreotide also shows activity against non-endocrine tumors, and, along with other somatostatin analogues, is being studied as a possible general antitumor agent. [4] [5]

In December 2014, the US FDA approved lanreotide for the treatment of people with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). [6]

It is used for polycystic liver disease.[ medical citation needed ] It has also been shown that it reduces the volume by 264mls on average.[ medical citation needed ]

Side effects

The main side effects of lanreotide treatment are mild to moderate pain at the injection site and gastrointestinal disturbances, such as diarrhea, nausea and vomiting. Isolated cases of gallstone formation have been associated with use of lanreotide, particularly over long periods of time. [3]

Pharmacology

Lanreotide is a synthetic analogue of somatostatin, a naturally occurring inhibitory hormone which blocks the release of several other hormones, including growth hormone, thyroid-stimulating hormone (TSH), insulin and glucagon. Lanreotide binds to the same receptors as somatostatin, although with higher affinity to peripheral receptors, and has similar activity. However, while somatostatin is quickly broken down in the body (within minutes), [7] lanreotide has a much longer half-life, and produces far more prolonged effects.[ medical citation needed ]

Formulations

Lanreotide is available in two formulations: a sustained release formulation (sold under the trade name 'Somatuline LA'), which is injected intramuscularly every ten or fourteen days, [3] and an extended release formulation (UK trade name 'Somatuline Autogel', or 'Somatuline Depot' in the US), which is administered subcutaneously once a month. [8]

Self-assembling properties

Lanreotide has been shown to spontaneously self-assemble into monodisperse nanotubes of 24.4 nm diameter [9] and has been thereafter used as a fruitful and versatile model system in several biophysical studies.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Growth hormone</span> Peptide hormone that stimulates growth

Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of insulin-like growth factor 1 (IGF-1) and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Somatostatin</span> Peptide hormone that regulates the endocrine system

Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.

<span class="mw-page-title-main">Pituitary adenoma</span> Tumor of the pituitary gland

Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%.

<span class="mw-page-title-main">Octreotide</span> Octapeptide that mimics natural somatostatin pharmacologically

Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer, and binds predominantly to the somatostatin receptors SSTR2 and SSTR5.

<span class="mw-page-title-main">Carcinoid</span> Slow-growing type of neuroendocrine tumor

A carcinoid is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut are associated with carcinoid syndrome.

Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to neuroendocrine tumors. The syndrome is caused by neuroendocrine tumors most often found in the gut releasing biologically active substances into the blood causing symptoms such as flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction.

<span class="mw-page-title-main">Hyperpituitarism</span> Medical condition

Hyperpituitarism is a condition due to the primary hypersecretion of pituitary hormones; it typically results from a pituitary adenoma. In children with hyperpituitarism, disruption of growth regulation is rare, either because of hormone hypersecretion or because of manifestations caused by local compression of the adenoma.

<span class="mw-page-title-main">Neuroendocrine tumor</span> Tumors of the endocrine and nervous systems

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body.

<span class="mw-page-title-main">Sermorelin</span> Pharmaceutical drug

Sermorelin acetate, also known as GHRH (1-29), is a peptide analogue of growth hormone-releasing hormone (GHRH) which is used as a diagnostic agent to assess growth hormone (GH) secretion for the purpose of diagnosing growth hormone deficiency. It is a 29-amino acid polypeptide representing the 1–29 fragment from endogenous human GHRH, thought to be the shortest fully functional fragment of GHRH.

<span class="mw-page-title-main">Somatostatin receptor 2</span> Protein-coding gene in the species Homo sapiens

Somatostatin receptor type 2 is a protein that in humans is encoded by the SSTR2 gene.

Pegvisomant, sold under the brand name Somavert, is a growth hormone receptor antagonist used in the treatment of acromegaly. It is primarily used if the pituitary gland tumor causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful, but is also effective as a monotherapy. It is delivered as a powder that is mixed with water and injected under the skin.

<span class="mw-page-title-main">Acromegaly</span> Human disease that results in excess growth of certain parts of the body

Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.

Indium-111 (111In) is a radioactive isotope of indium (In). It decays by electron capture to stable cadmium-111 with a half-life of 2.8 days. Indium-111 chloride (111InCl) solution is produced by proton irradiation of a cadmium target in a cyclotron, as recommended by International Atomic Energy Agency (IAEA). The former method is more commonly used as it results in a high level of radionuclide purity.

<span class="mw-page-title-main">DOTA-TATE</span> Eight amino-acid long peptide covalently bonded to a DOTA chelator

DOTA-TATE is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.

<span class="mw-page-title-main">Edotreotide</span> Chemical compound

Edotreotide (USAN, also known as (DOTA0-Phe1-Tyr3) octreotide, DOTA-TOC, DOTATOC) is a substance which, when bound to various radionuclides, is used in the treatment and diagnosis of certain types of cancer. When used therapeutically it is an example of peptide receptor radionuclide therapy.

Advanced Accelerator Applications is a France-based pharmaceutical group, specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine to diagnose and treat serious conditions in the fields of oncology, neurology, cardiology, infectious and inflammatory diseases.

<span class="mw-page-title-main">Pancreatic neuroendocrine tumor</span> Tumors of the nervous or endocrine system within the pancreas

Pancreatic neuroendocrine tumours, often referred to as "islet cell tumours", or "pancreatic endocrine tumours" are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within the pancreas.

<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Lutetium (<sup>177</sup>Lu) oxodotreotide Chelate of Lu-177 with dotatate, a peptide derivative bound to a DOTA molecule

Lutetium (177Lu) oxodotreotide (INN) or 177Lu dotatate, brand name Lutathera, is a chelated complex of a radioisotope of the element lutetium with dotatate, used in peptide receptor radionuclide therapy. Specifically, it is used in the treatment of cancers which express somatostatin receptors. It is a radiolabeled somatostatin analog.

References

  1. ↑ "Mytolac (Amdipharm Mercury Australia Pty Ltd)". Therapeutic Goods Administration (TGA). 28 September 2022. Archived from the original on 13 November 2022. Retrieved 29 April 2023.
  2. ↑ "FDA Approves New Drug to Treat Rare Disease, Acromegaly" (Press release). U.S. Food and Drug Administration. 30 August 2007. Archived from the original on 10 April 2021. Retrieved 6 September 2007.
  3. 1 2 3 "Somatuline LA". electronic Medicines Compendium. 17 September 2003. Archived from the original on 24 September 2006. Retrieved 2 March 2007.
  4. ↑ Kvols L, Woltering E (2006). "Role of somatostatin analogs in the clinical management of non-neuroendocrine solid tumors". Anticancer Drugs. 17 (6): 601–8. doi:10.1097/01.cad.0000210335.95828.ed. PMID   16917205.
  5. ↑ Susini C, Buscail L (2006). "Rationale for the use of somatostatin analogs as antitumor agents". Ann Oncol. 17 (12): 1733–42. doi: 10.1093/annonc/mdl105 . PMID   16801334.
  6. ↑ "FDA Approves Lanreotide Injection for GEP-NETs". 2014. Archived from the original on 26 June 2019. Retrieved 29 April 2023.
  7. ↑ Rens-Domiano S, Reisine T (1992). "Biochemical and functional properties of somatostatin receptors". J Neurochem. 58 (6): 1987–96. doi:10.1111/j.1471-4159.1992.tb10938.x. PMID   1315373. S2CID   36873846.
  8. ↑ "Somatuline Autogel". electronic Medicines Compendium. 12 April 2007. Archived from the original on 28 September 2007. Retrieved 19 April 2007.
  9. ↑ Valéry C, Paternostre M, Robert B, Gulik-Krzywicki T, Narayanan T, Dedieu JC, Keller G, Torres ML, Cherif-Cheikh R, Calvo P, Artzner F (2003). "Biomimetic organization: Octapeptide self-assembly into nanotubes of viral capsid-like dimension". Proceedings of the National Academy of Sciences of the United States of America. 100 (18): 10258–62. Bibcode:2003PNAS..10010258V. doi: 10.1073/pnas.1730609100 . PMC   193548 . PMID   12930900.
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