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H-Dnal-Cyclo[Cys-Tyr-Dtrp-Lys-Val-Dcys]-Thr-Nh2

Basic information

CPKB ID CP01243
IUPAC Name
(4R,7S,10R,13S,16R,19S)-10-(4-aminobutyl)-N-[(2S)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2R)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
Synonyms
Bdbm50063821
Chembl414254
H-Dnal-Cyclo[Cys-Tyr-Dtrp-Lys-Val-Dcys]-Thr-Nh2
H-Dnal-Cyclo[Dcys-Tyr-Dtrp-Lys-Val-Cys]-Thr-Nh2
Lanreotide
Source

Synthetic construct [Division : Synthetic]

Wikipedia: Synthetic construct

PubChem  

Function

Growth Hormone Inhibitor   PubChem  

Information

Lanreotide is a synthetic polypeptide analogue of somatostatin that resembles the native hormone in its ability to suppress levels and activity of growth hormone, insulin, glucagon and many other gastrointestinal peptides. Because its half-life is longer than somatostatin, lanreotide can be used clinically to treat neuroendocrine tumors that secrete excessive amounts of growth hormone (acromegaly) or other active hormones or neuropeptides. Lanreotide has many side effects including suppression of gall bladder contractility and bile production, and maintenance therapy may cause cholelithiasis and pancreatitis as well accompanying liver injury.

PubChem|44270249  

Legend

Structure

Download structure
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similarity structure
Molecular Formula

C54H69N11O10S2
Molecular Weight 1095.467029 g/mol
SMILES

RUN SEA Predictions

 CC(C)[C@@H]1NC(=O)[C@@H](CCCCN)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](NC(=O)[C@H](N)Cc2ccc3ccccc3c2)CSSC[C@@H](C(=O)N[C@H](C(N)=O)C(C)O)NC1=O  

PubChem|44270249
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)/t30?,38-,40-,41-,42+,43-,44+,45+,46+/m1/s1  
InChIKey
PUDHBTGHUJUUFI-BPGAYHOPNA-N
2D Structure
PubChem|44270249

Sequence

Graph alignment
Local alignment
IUPAC Condensed
H-D-2Nal-D-Cys(1)-D-Tyr-Trp-D-Lys-Val-Cys(1)-xiThr-NH2  

PubChem|44270249
Amino acid chain
H-D-2Nal--D-Cys(1)--D-Tyr--Trp--D-Lys--Val--Cys(1)--xiThr-NH2  

CyclicPepedia|PP
Graph representation
H-D-2Nal,D-Cys,D-Tyr,Trp,D-Lys,Val,Cys,xiThr-NH2 @1,6  

CyclicPepedia|PP
One letter code from Structure
FCYWKVCT  

CyclicPepedia|Struct2seq
Amino acid chain from Structure
Phe--Cys(1)--Tyr--Trp--Lys--Val--Cys(1)--Eta  

CyclicPepedia|Struct2seq
Description of the conversion sequence The one letter code and Amino acid chain derived from the structural transformation may be inconsistent, with the Amino acid chain containing Essential Amino acid and the one letter code not.
svg Image

PubChem|44270249

Chemical and Physical Properties

CyclicPepedia|Struc2Seq + PP

Structure Properties

Property Name Property Value
Exact Mass 1095.467029
Number of Rings 6.0
Complexity 0.714285714
XlogP3 AA 0.8216
Heavy Atom Count 77.0
Hydrogen Bond Donor Count 13.0
Hydrogen Bond Acceptor Count 14.0
Rotatable Bond Count 17.0
Property Name Property Value
Formal Charge 0.0
Refractivity 296.4904
Rule_of_Five 0.0
Number of Atoms 77.0
Topological Polar Surface Area 355.08
Refractivity 296.4904
Veber Rule 0.0
Ghose Filter 0.0
Property Name Property Value
RDKit Fingerprint
11000111110110100111010011110000111000100111100000011011101001101110101111101110111111010100100011110101110101001010011011110111010001011000111100001111000010010100001000111111100111001111000101110100101001001000000110000001010101000101010110001110011101101111000110001110001110101111110000000010000001011111100111010001110100000011111110111110011100000000111100001001000001010010001001101010010100000111000100001111000010110001101000111111110010100000110000010110111000011000000100001110001101000111100100101111111101011110110110001101101010101101100001010110101001100110010010001001000110111000101110010001101010011010110000111111110100111100100111110111011001000110111110111111010111001001011100110000101101100000000111000010101111001111101010110010001110101011100110011000001111001001011010011011001100011011100100001101111011110000011011111101111001110111011101111011010110000101001000000011001101101110111100110110011100110010110001011101101010011011111100010000011001010110001001110001110101000101000000111101111111110111110110111111110001001011000101001110101001100001100001000001110110000101001101001010000001101001100011101101110010010100101000011000101010110100101111001001010011111110111011000000100001001101110011100100011101110111010010011001101111000110101110001010100001111000110100001001011010111101100111010111101001001011111111010000011110110011110010110001111101001111001000000111100101001100000011100101101011001000011001111100100101001011100110101110010101110001110000111011001011010000100100100011111011110101011000010100011111110100110101100000100110100101001011010111100010000011100110101011010010100000010110100000000000100010010010001010001011000110101011100100000010110101111110100110100101000101010110101000100000100011011001011101111010010110100010001000100001111010100011110011111111101100100101111010111110100111111011000001100001010000011011101010010100001101101010010100101101100011011011010111001110010111110110100011011001011101011001001011101101100111000101111100110110011000000011101100010100100100111001010011
Morgan Fingerprint
0100000000100000000000000000000001000000000000000000000000100001100000000000000110000000001000100000000000000000000101010000000010000000000010000001000000000000100000000000000100000000000010000000000000010000000000001000100000010000000000000000100000000100000000000000000000000000001100000100000000000100000000100010000000100100100001100000000000000100000110000011100000000000000000000001000000000000001000000000000000000000000000001001000000000000000000000110000000000000001000100010000000001100000000000000010000000001100000000000000000000000000001000000000000000000000001000010000100000000000000100000000010000000000000000000000000000000000000000010000000000000010001000001000000000000010000000000000000000001000000000000001000100000000000000100000000100001000000000000000000000000001000000000000000001011000010001000000001001001110000000000000001000001000000000000000000010000000000010000010000010000000000000100010000000010000000000000000000000000000001000000001000000000100001000000000000000000000000100000000001010000
MACCS Keys
00000000000000100000000000000000000010000000000000000110000000000101000000100001001110001111100111001100110000110100011011001101010101001111111101110111111111111111110

Sequence Properties

Property Name Property Value
Boman Index -0.45625
Instability 25.925
Charge 0.872889419471714
Aliphatic Index 36.25

Binding Target

Other evidence

Property Name Property ID
TTD D0M2YE
DrugMAP DMG6ZU4

Biologic Description

Toxicity PubChem|44270249

In preregistration studies of lanreotide, serum enzyme levels did not change appreciably and there were no reports of clinically apparent acute liver injury. Pooled analyses reported that there were no overall changes in serum ALT, AST or alkaline phosphatase levels during therapy or instances of clinically meaningful elevations with treatment. Prolonged therapy with lanreotide, as with other somatostatin analogues, was associated with a high rate of biliary sludge and cholelithiasis, probably due to inhibition of gall bladder contractility and decrease in bile secretion. In long term studies, cholelithiasis developed in 20% to 33% of lanreotide treated patients. In some instances, symptomatic cholecystitis occurred which can be accompanied by mild-to-moderate elevations in serum enzymes and bilirubin. However, most lanreotide associated gallstones were asymptomatic. Unlike octreotide, lanreotide and other long acting somatostatin analogues have not been liked to cases of clinically apparent liver injury, independent of cholelithiasis or biliary sludge, although they have had more limited use and have not been used in many of the clinical situations that were treated with octreotide (portal hypertension, variceal hemorrhage and infants with congenital hyperinsulinemia).

Manufacturers

Forecasting tools

Information Source

Reference

Pubmed_ID Title DOI Journal

19071884

 Population pharmacokinetic analysis of lanreotide Autogel in healthy subjects : evidence for injection interval of up to 2 months 10.2165/0003088-200948010-00004.

Clin Pharmacokinet

Population pharmacokinetic analysis of lanreotide Autogel in healthy subjects : evidence for injection interval of up to 2 months

Abstract

  • Lanreotide is a somatostatin analogue used for the treatment of acromegaly and neuroendocrine tumours. The objective of this study was to develop a pharmacokinetic model for the sustained-release formulation lanreotide Autogel after deep subcutaneous administration in healthy subjects, and to explore the potential effect of covariates, especially sex and dose. This was an open-label, single-centre, randomized, dose-ranging, parallel-group study, with a follow-up period of 4-7 months following drug administration in healthy subjects. Healthy Caucasian subjects aged 18-45 years were included. Subjects received a rapid intravenous bolus of 7 microg/kg of an immediate-release formulation of lanreotide (lanreotide IRF). After a 3-day washout period, participants were randomized to receive a single deep subcutaneous injection of lanreotide Autogel at a dose of 60, 90 or 120 mg. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Blood samples for lanreotide determination were obtained during the first 12 hours after the intravenous bolus injection and during the 4- to 7-month follow-up period after deep subcutaneous administration of lanreotide Autogel. Data after intravenous and subcutaneous administration were fitted simultaneously using the population approach in NONMEM((R)) version VI software. The model was validated externally using data from patients with acromegaly. In total, 50 healthy subjects (24 women and 26 men) received a single intravenous dose of lanreotide IRF. Of these, 38 subjects (18 women and 20 men) received a single subcutaneous dose of lanreotide Autogel 3 days after intravenous lanreotide IRF. The disposition of lanreotide was described by a three-compartment open model. The estimates of the total volume of distribution and serum clearance were 15.1 L and 23.1 L/h, respectively. The estimates of interindividual variability were <40%. To evaluate lanreotide Autogel pharmacokinetics, the absorption rate was modelled to decrease exponentially as a function of the natural logarithm of time. The absolute bioavailability after deep subcutaneous administration of lanreotide Autogel was 63%. The rate of absorption and bioavailability of lanreotide Autogel were independent of the administered dose in the range from 60 to 120 mg, and no significant effect of covariates (sex, dose, age or bodyweight) was found (p > 0.05). Population analysis allows a full description of the disposition of lanreotide after rapid intravenous bolus administration of lanreotide IRF (7 microg/kg) and the pharmacokinetics of lanreotide Autogel after a single deep subcutaneous injection (60, 90 or 120 mg) in healthy subjects. The model-based simulations provide support for the feasibility of extending the dosing interval for lanreotide Autogel to 56 days when given at 120 mg. The absorption profile of lanreotide Autogel was independent of the dose and was not affected by sex.

25060168

 Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors 10.1517/13543784.2014.942728.

Expert Opin Investig Drugs

Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors

Abstract

  • Octreotide long-acting release (LAR) and lanreotide Autogel (ATG) are the two somatostatin analogs currently approved for treatment of acromegaly and neuroendocrine tumors (NETs). The strength of these drugs has been their specificity for somatostatin receptor subtype 2. However, this peculiarity may become a weakness in some patients with tumors harboring somatostatin receptors different from the subtype 2. Another clinically relevant aspect related to the use of octreotide LAR and lanreotide ATG is the burden of injectable drug regimen that may adversely impact the quality of life of patients with acromegaly and NETs. The authors review the recently published evidence on novel drugs targeting somatostatin receptors developed for treating acromegaly and NETs. Within this article, the authors discuss: i) the pharmacology of somatostatin and traditional somatostatin analogs; ii) the efficacy and safety of multireceptor-targeted somatostatin analogs in acromegaly and NETs; iii) the efficacy of chimeric molecules in acromegaly and NETs; iv) the preliminary data on the use of new injectable, oral and transdermal formulations of octreotide in acromegaly. The development of new somatostatin analogs and new formulations has opened a new scenario for treatment of acromegaly and NETs. That being said, even though there have been big steps taken in the development of new therapies for acromegaly, there are still a number of unresolved issues, while more trials are necessary for the use of somatostatin anaologs in the treatment of NETs.

25307803

 Lanreotide autogel in acromegaly - a decade on 10.1517/14656566.2014.970173.

Expert Opin Pharmacother

Lanreotide autogel in acromegaly - a decade on

Abstract

  • The novel formulation of lanreotide, lanreotide (LAN) autogel (ATG), has been available in Europe since 2001 and USA from 2006 for the treatment of acromegaly. It is one of only two clinically available somatostatin analogs available for use in acromegaly. Data relating to the use of ATG in acromegaly, specifically relating to comparison to octreotide (OCT) LAR and patient acceptability and preference, have been slow to accumulate. We performed a comprehensive review of the original literature relating to development, pharmacokinetics, acceptability and clinical efficacy of ATG. LAN ATG is a novel formulation of LAN consequent on self-assembly of nanotubules in water. Diffusion between molecules within the nanotubules and surrounding tissue fluid in vivo leads to pseudo first-order pharmacokinetics. Efficacy is equivalent to the alternate long-acting somatostatin analog, OCT LAR, normalizing growth hormone and IGF-I levels in around 60 and 50% respectively. Control of tumor growth is observed in over 95% of patients, with 64% seeing a clinically significant reduction in tumor size. ATG is provided in a prefilled syringe for deep subcutaneous injection, allowing self-injection, and may be administered up to 8 weeks greatly improving convenience for the patient. The data strongly support consideration of ATG as the medical therapy of choice for patients with acromegaly.

26614375

 Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors 10.1016/j.hoc.2015.09.008.

Hematol Oncol Clin North Am

Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors

Abstract

  • Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation originating most commonly in the lungs and gastroenteropancreatic. Treatment includes surgery and other local therapies; treatment of inoperable disease centers around symptom management and control of tumor growth. Somatostatin analogues (SSAs) have been a mainstay of managing hormone-related symptoms. Emerging evidence suggests that they are effective therapies for tumor control also. Peptide receptor radionuclide therapy with radiolabeled SSAs is a new, promising treatment for inoperable or metastatic NETs. This article reviews the role of SSAs in the treatment of NETs.