Identification

Name
Lanreotide
Accession Number
DB06791
Type
Small Molecule
Groups
Approved
Description

Lanreotide (INN) 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. Its sequence is H-D-2Nal-Cys(1)-Tyr-D-Trp-Lys-Val-Cys(1)-Thr-NH2. Lanreotide (as lanreotide acetate) is manufactured by Ipsen, and marketed under the trade name Somatuline. 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.

Structure
Thumb
Synonyms
  • Lanreotida
External IDs
BIM-23014C
Product Ingredients
IngredientUNIICASInChI Key
Lanreotide acetateIEU56G3J9CNot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Somatuline AutogelSolution, gel forming, extended release60 mgSubcutaneousIpsen Biopharm Limited2007-02-22Not applicableCanada
Somatuline AutogelSolution, gel forming, extended release120 mgSubcutaneousIpsen Biopharm Limited2007-02-22Not applicableCanada
Somatuline AutogelSolution, gel forming, extended release90 mgSubcutaneousIpsen Biopharm Limited2007-02-22Not applicableCanada
Somatuline DepotInjection60 mg/0.2mLSubcutaneousIpsen Biopharmaceuticals, Inc.2007-11-142016-08-31Us
Somatuline DepotInjection120 mg/0.5mLSubcutaneousIpsen Biopharmaceuticals, Inc.2007-11-14Not applicableUs
Somatuline DepotInjection120 mg/0.5mLSubcutaneousIpsen Biopharmaceuticals, Inc.2007-11-142016-08-31Us
Somatuline DepotInjection90 mg/0.3mLSubcutaneousIpsen Biopharmaceuticals, Inc.2007-11-14Not applicableUs
Somatuline DepotInjection90 mg/0.3mLSubcutaneousIpsen Biopharmaceuticals, Inc.2007-11-142016-08-31Us
Somatuline DepotInjection60 mg/0.2mLSubcutaneousIpsen Biopharmaceuticals, Inc.2007-11-14Not applicableUs
International/Other Brands
Somatuline (Ipsen)
Categories
UNII
0G3DE8943Y
CAS number
108736-35-2
Weight
Average: 1096.33
Monoisotopic: 1095.467029814
Chemical Formula
C54H69N11O10S2
InChI Key
PUDHBTGHUJUUFI-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-({19-[2-amino-3-(naphthalen-2-yl)propanamido]-10-(4-aminobutyl)-16-[(4-hydroxyphenyl)methyl]-13-[(1H-indol-3-yl)methyl]-6,9,12,15,18-pentaoxo-7-(propan-2-yl)-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}formamido)-3-hydroxybutanamide
SMILES
[H]N([H])CCCCC1N([H])C(=O)C(CC2=CN([H])C3=CC=CC=C23)N([H])C(=O)C(CC2=CC=C(O)C=C2)N([H])C(=O)C(CSSCC(N([H])C(=O)C(N([H])C1=O)C(C)C)C(=O)N([H])C(C(C)O)C(=O)N([H])[H])N([H])C(=O)C(CC1=CC2=CC=CC=C2C=C1)N([H])[H]

Pharmacology

Indication

Lanreotide is a somatostatin analog approved for treatment of neuroendocrine tumours and acromegaly. (2)

Associated Conditions
Pharmacodynamics

Lanreotide exhibits antisecretory effects through cAMP suppression, and activation of ion currents such as K+ and Ca2+ which leads to hyperpolarization of the membrane and inhibition of Ca2+ mediated depolarization. Furthermore, through direct and indirect mechanisms, Lanreotide has potent antiproliferative effects. (2)

Mechanism of action

Lanreotide is a somatostatin analogue (SSA) and has mainly inhibitory effects which are mediated via somatostatin receptors (SSTRs) 2 and 5 and include inhibition of growth hormone release in the brain. Tumor SSTR activation induces downstream cell cycle arrest and/or apoptosis, and also results in blunted production of substances that support tumor growth as well as tumor angiogenesis. This leads to the anti-proliferative effects of Lanreotide. (3)

TargetActionsOrganism
USomatostatin receptor type 2
agonist
Human
USomatostatin receptor type 5
agonist
Human
Absorption

Lanreotide forms a drug depot at the site of injection (4); therefore, there are 2 phases that describe the absorption of Lanreotide: 1. Initial rapid subcutaneous release during the first few days of treatment where drug that has not precipitated is rapidly absorbed.
2. Slow release of drug from the depot via passive diffusion. (1) Absorption is independent of body weight, gender, and dosage. (5)

Volume of distribution

Estimated Volume of Distribution = 15.1 L (1)

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

<5% of lanreotide is excreted in urine, and less than 0.5% is excreted unchanged in the feces suggesting biliary excretion involvement. (4)

Half life

Half-life is approximately 22 days (5)

Clearance

Estimated Clearance = 23.1 L/h (1)

Toxicity

The most common adverse events are GI related, occurring in 67-84% of patients, and are typically mild to moderate. GI related effects are often transient, improve with subsequent injections, and most frequently include diarrhea and abdominal pain. Other GI symptoms such as nausea, vomiting, and abdominal distension are less common. It is not clear whether or not GI effects are dose related. Adverse effects relating to site of injection occur in 43% of patients and are more common in patients who self-inject as opposed to those who had health-care professionals administer the injection. A small number of patients report newly impaired glucose tolerance, fasting glucose or diabetes mellitus. Patients being treated for diabetes mellitus may experience hypoglycemia. After 1 year, up to 30% of patients may experience gallstone formation and the presence of sludge within the gallbladder due to inhibition of gallbladder and GI motility. This may be influenced by previous exposure to somatostatin analogues. Other adverse effects include reduction in left ventricular end-diastolic and end-systolic volumes, bradycardia, nasopharyngitis, and alopecia. (5) Lanreotide is classified as Pregnancy Category C. (4)

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lanreotide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lanreotide.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Lanreotide.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lanreotide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lanreotide.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Lanreotide.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Lanreotide.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Lanreotide.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Lanreotide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Lanreotide.
Food Interactions
Not Available

References

General References
  1. Troconiz IF, Cendros JM, Peraire C, Ramis J, Garrido MJ, Boscani PF, Obach R: Population pharmacokinetic analysis of lanreotide Autogel in healthy subjects : evidence for injection interval of up to 2 months. Clin Pharmacokinet. 2009;48(1):51-62. doi: 10.2165/0003088-200948010-00004. [PubMed:19071884]
  2. Giustina A, Mazziotti G, Maffezzoni F, Amoroso V, Berruti A: Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors. Expert Opin Investig Drugs. 2014 Dec;23(12):1619-35. doi: 10.1517/13543784.2014.942728. Epub 2014 Jul 25. [PubMed:25060168]
  3. Narayanan S, Kunz PL: Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors. Hematol Oncol Clin North Am. 2016 Feb;30(1):163-77. doi: 10.1016/j.hoc.2015.09.008. [PubMed:26614375]
  4. Kyriakakis N, Chau V, Lynch J, Orme SM, Murray RD: Lanreotide autogel in acromegaly - a decade on. Expert Opin Pharmacother. 2014 Dec;15(18):2681-92. doi: 10.1517/14656566.2014.970173. Epub 2014 Oct 11. [PubMed:25307803]
External Links
KEGG Drug
D04666
PubChem Compound
71349
PubChem Substance
310264887
ChemSpider
64450
ChEMBL
CHEMBL1201185
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Lanreotide
ATC Codes
H01CB03 — Lanreotide
AHFS Codes
  • 92:92.00 — Other Miscellaneous Therapeutic Agents
FDA label
Download (418 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentNeuroendocrine Tumors1
1, 2CompletedTreatmentAcromegaly1
1, 2RecruitingTreatmentGastroenteropancreatic Neuroendocrine Tumors1
2Active Not RecruitingTreatmentCarcinoid Tumors1
2Active Not RecruitingTreatmentCarcinoid Tumors / Neoplasms, Gastrointestinal / Neuroendocrine Tumors1
2Active Not RecruitingTreatmentNeuroendocrine Tumours1
2CompletedSupportive CareIntestinal Obstruction2
2CompletedTreatmentMalignant Intestinal Obstruction1
2CompletedTreatmentNeuroendocrine Carcinoma of the Skin1
2CompletedTreatmentNeuroendocrine Tumours1
2RecruitingPreventionPancreatectomy; Hyperglycemia / Pancreatic Fistula / Pancreatic leak / Pancreaticoduodenal; Fistula1
2RecruitingTreatmentCarcinoid Tumors1
2RecruitingTreatmentIntestinal Diseases / Upper gastrointestinal motility disorders1
2Unknown StatusTreatmentAcid Reflux Esophagitis / Non-acid Reflux Esophagitis1
2WithdrawnTreatmentAcromegaly1
2, 3CompletedTreatmentAcromegaly1
2, 3CompletedTreatmentAdvanced Hepatocellular Carcinoma1
2, 3CompletedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD) / Hepatomegaly / Liver Diseases / Polycystic Liver Disease (PLD)1
2, 3CompletedTreatmentSevere or persistent diarrhea1
2, 3RecruitingTreatmentMetastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours1
2, 3Unknown StatusTreatmentAutosomal Dominant / Hepatomegaly / Kidney, Polycystic / Liver Diseases / Polycystic Liver Disease (PLD)1
3Active Not RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)2
3Active Not RecruitingTreatmentNeuroendocrine Tumors1
3CompletedTreatmentAbdominal wall neoplasm / Carcinoma NOS / Intestinal Obstruction1
3CompletedTreatmentAcromegaly4
3CompletedTreatmentCarcinoid Syndrome1
3CompletedTreatmentEndocrine Tumors1
3CompletedTreatmentNon Functioning Entero-pancreatic Endocrine Tumour1
3Not Yet RecruitingTreatmentAcromegaly Due to Pituitary Adenoma1
4CompletedDiagnosticNeuroendocrine Tumours1
4CompletedTreatmentAcromegaly2
4CompletedTreatmentNeuroendocrine Tumour With Carcinoid Symptoms1
4RecruitingTreatmentNeuroendocrine Tumors1
4TerminatedTreatmentAcromegaly1
4Unknown StatusTreatmentCongenital Hyperinsulinism1
4Unknown StatusTreatmentDumping Syndrome1
Not AvailableCompletedNot AvailablePolycystic Liver Disease (PLD)1
Not AvailableRecruitingNot AvailableAcromegaly1
Not AvailableRecruitingNot AvailableHepatocellular,Carcinoma / Neuroendocrine Tumors1
Not AvailableRecruitingTreatmentAcromegaly1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Solution, gel forming, extended releaseSubcutaneous120 mg
Solution, gel forming, extended releaseSubcutaneous60 mg
Solution, gel forming, extended releaseSubcutaneous90 mg
InjectionSubcutaneous120 mg/0.5mL
InjectionSubcutaneous60 mg/0.2mL
InjectionSubcutaneous90 mg/0.3mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5595760No1997-01-212020-03-08Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00496 mg/mLALOGPS
logP1.87ALOGPS
logP-0.33ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)9.43ChemAxon
pKa (Strongest Basic)10.26ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area355.08 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity292.92 m3·mol-1ChemAxon
Polarizability114.68 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / N-acyl-alpha amino acids and derivatives / Macrolactams / Alpha amino acid amides / 3-alkylindoles / Naphthalenes / 1-hydroxy-2-unsubstituted benzenoids / Aralkylamines / Substituted pyrroles / Benzene and substituted derivatives
show 13 more
Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Macrolactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Naphthalene / 3-alkylindole / Indole or derivatives
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and ...
Gene Name
SSTR2
Uniprot ID
P30874
Uniprot Name
Somatostatin receptor type 2
Molecular Weight
41332.37 Da
References
  1. Buil-Bruna N, Garrido MJ, Dehez M, Manon A, Nguyen TX, Gomez-Panzani EL, Troconiz IF: Population Pharmacokinetic Analysis of Lanreotide Autogel((R))/Depot in the Treatment of Neuroendocrine Tumors: Pooled Analysis of Four Clinical Trials. Clin Pharmacokinet. 2016 Apr;55(4):461-73. doi: 10.1007/s40262-015-0329-4. [PubMed:26416534]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition act...
Gene Name
SSTR5
Uniprot ID
P35346
Uniprot Name
Somatostatin receptor type 5
Molecular Weight
39201.925 Da
References
  1. Buil-Bruna N, Garrido MJ, Dehez M, Manon A, Nguyen TX, Gomez-Panzani EL, Troconiz IF: Population Pharmacokinetic Analysis of Lanreotide Autogel((R))/Depot in the Treatment of Neuroendocrine Tumors: Pooled Analysis of Four Clinical Trials. Clin Pharmacokinet. 2016 Apr;55(4):461-73. doi: 10.1007/s40262-015-0329-4. [PubMed:26416534]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on September 14, 2010 10:21 / Updated on November 17, 2018 07:22