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H-Dphe-Cyclo[Dpen-Tyr-Dtrp-Lys-Val-Cys]-Thr-Nh2

Basic information

CPKB ID CP00778
IUPAC Name
(4S,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-N-[(2S,3R)-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
108736-35-2
Bdbm50063830
Chembl2079626
H-Dphe-Cyclo[Dpen-Tyr-Dtrp-Lys-Val-Cys]-Thr-Nh2
Lanreotide
S6948
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|10796238  

Legend

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@@H](C)O)NC1=O  

PubChem|10796238
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-DQRTXKFUNA-N
2D Structure
PubChem|10796238

Sequence

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

PubChem|10796238
Amino acid chain
H-D-2Nal--Cys(1)--Tyr--D-Trp--Lys--Val--D-Cys(1)--Thr-NH2  

CyclicPepedia|PP
Graph representation
H-D-2Nal,Cys,Tyr,D-Trp,Lys,Val,D-Cys,Thr-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|10796238

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|10796238

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

18444611

 Coibamide A, a potent antiproliferative cyclic depsipeptide from the Panamanian marine cyanobacterium Leptolyngbya sp 10.1021/ja801383f.

J Am Chem Soc

Coibamide A, a potent antiproliferative cyclic depsipeptide from the Panamanian marine cyanobacterium Leptolyngbya sp

Abstract

  • Coibamide A (1) is a new, potent antiproliferative depsipeptide which was isolated from a marine Leptolyngbya cyanobacterium collected from the Coiba National Park, Panama. The planar structure of 1 was elucidated by a combination of NMR spectroscopy and mass spectrometry. Exhaustive 1D and 2D NMR spectroscopy included natural abundance 15N and variable temperature experiments; mass spectrometry included TOF-ESI-MSn and FT-MSn experiments. Chemical degradation followed by chiral HPLC- and GC-MS analyses was used to assign the absolute configuration of 1. This highly methylated cyclized depsipeptide exhibited an unprecedented selectivity profile in the NCI 60 cancer cell line panel and appears to act via a novel mechanism.

23762328

 Coibamide A induces mTOR-independent autophagy and cell death in human glioblastoma cells 10.1371/journal.pone.0065250.

PLoS One

Coibamide A induces mTOR-independent autophagy and cell death in human glioblastoma cells

Abstract

  • Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative of a unique mechanism of action. We report that coibamide A is a more potent and efficacious cytotoxin than was previously appreciated, inducing concentration- and time-dependent cytotoxicity (EC50<100 nM) in human U87-MG and SF-295 glioblastoma cells and mouse embryonic fibroblasts (MEFs). This activity was lost upon linearization of the molecule, highlighting the importance of the cyclized structure for both anti-proliferative and cytotoxic responses. We show that coibamide A induces autophagosome accumulation in human glioblastoma cell types and MEFs via an mTOR-independent mechanism; no change was observed in the phosphorylation state of ULK1 (Ser-757), p70 S6K1 (Thr-389), S6 ribosomal protein (Ser-235/236) and 4EBP-1 (Thr-37/46). Coibamide A also induces morphologically and biochemically distinct forms of cell death according to cell type. SF-295 glioblastoma cells showed caspase-3 activation and evidence of apoptotic cell death in a pattern that was also seen in wild-type and autophagy-deficient (ATG5-null) MEFs. In contrast, cell death in U87-MG glioblastoma cells was characterized by extensive cytoplasmic vacuolization and lacked clear apoptotic features. Cell death was attenuated, but still triggered, in Apaf-1-null MEFs lacking a functional mitochondria-mediated apoptotic pathway. From the study of ATG5-null MEFs we conclude that a conventional autophagy response is not required for coibamide A-induced cell death, but likely occurs in dying cells in response to treatment. Coibamide A represents a natural product scaffold with potential for the study of mTOR-independent signaling and cell death mechanisms in apoptotic-resistant cancer cells.

25488840

 Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A 10.1016/j.bmcl.2014.11.044.

Bioorg Med Chem Lett

Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A

Abstract

  • Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the resin and its subsequent macrolactonization. The peptide sequence of the linear coibamide A precursor was constructed on a solid-support following the optimization of the coupling conditions, where numerous coupling agents were evaluated. The macrocyclization of the resulting linear peptide provided the [d-MeAla(11)]-epimer of coibamide A, which exhibited nanomolar cytotoxic activity towards a number of human cancer cell lines.