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Identification
NameVapreotide
Accession NumberDB04894
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionVapreotide is a synthetic octapeptide somatostatin analog. It was being studied for the treatment of cancer.
Structure
Thumb
Synonyms
Vapreotida
Vapreotidum
External Identifiers
  • BMY 41606
  • BMY-41606
  • RC-160
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
OctastatinNot Available
SanvarNot Available
Sanvar IRNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Vapreotide acetate
849479-74-9
Thumb
  • InChI Key: KBIZSMHYSQUHDH-UHFFFAOYSA-N
  • Monoisotopic Mass: 1190.504143599
  • Average Mass: 1191.43
DBSALT000535
Categories
UNII2PK59M9GFF
CAS number103222-11-3
WeightAverage: 1131.38
Monoisotopic: 1130.48301423
Chemical FormulaC57H70N12O9S2
InChI KeySWXOGPJRIDTIRL-DOUNNPEJSA-N
InChI
InChI=1S/C57H70N12O9S2/c1-32(2)49-57(78)68-48(55(76)64-44(50(60)71)26-35-28-61-41-16-8-6-14-38(35)41)31-80-79-30-47(67-51(72)40(59)24-33-12-4-3-5-13-33)56(77)65-45(25-34-19-21-37(70)22-20-34)53(74)66-46(27-36-29-62-42-17-9-7-15-39(36)42)54(75)63-43(52(73)69-49)18-10-11-23-58/h3-9,12-17,19-22,28-29,32,40,43-49,61-62,70H,10-11,18,23-27,30-31,58-59H2,1-2H3,(H2,60,71)(H,63,75)(H,64,76)(H,65,77)(H,66,74)(H,67,72)(H,68,78)(H,69,73)/t40-,43+,44+,45+,46-,47+,48+,49+/m1/s1
IUPAC Name
(2R)-2-amino-N-[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-6,9,12,15,18-pentahydroxy-4-{[(1S)-1-(C-hydroxycarbonimidoyl)-2-(1H-indol-3-yl)ethyl]-C-hydroxycarbonimidoyl}-16-[(4-hydroxyphenyl)methyl]-13-[(1H-indol-3-yl)methyl]-7-(propan-2-yl)-1,2-dithia-5,8,11,14,17-pentaazacycloicosa-5,8,11,14,17-pentaen-19-yl]-3-phenylpropanimidic acid
SMILES
[H][C@@](N)(CC1=CC=CC=C1)C(O)=N[C@@]1([H])CSSC[C@]([H])(N=C(O)[C@@]([H])(N=C(O)[C@]([H])(CCCCN)N=C(O)[C@@]([H])(CC2=CNC3=CC=CC=C23)N=C(O)[C@]([H])(CC2=CC=C(O)C=C2)N=C1O)C(C)C)C(O)=N[C@@]([H])(CC1=CNC2=CC=CC=C12)C(O)=N
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentOligopeptides
Alternative Parents
Substituents
  • Alpha-oligopeptide
  • Cyclic alpha peptide
  • Phenylalanine or derivatives
  • Macrolactam
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Triptan
  • N-substituted-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Amphetamine or derivatives
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • 1-hydroxy-2-unsubstituted benzenoid
  • Aralkylamine
  • Phenol
  • Benzenoid
  • Substituted pyrrole
  • Monocyclic benzene moiety
  • Fatty acyl
  • Fatty amide
  • Pyrrole
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Primary carboxylic acid amide
  • Amino acid or derivatives
  • Organic disulfide
  • Carboxamide group
  • Lactam
  • Organoheterocyclic compound
  • Azacycle
  • Primary amine
  • Hydrocarbon derivative
  • Primary aliphatic amine
  • Carbonyl group
  • Organic nitrogen compound
  • Organic oxide
  • Organonitrogen compound
  • Amine
  • Organooxygen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of esophageal variceal bleeding in patients with cirrhotic liver disease and has also shown efficacy in the treatment of patients with AIDS-related diarrhea.
PharmacodynamicsVapreotide is a somatostatin analog with a higher metabolic stability than the parent hormone. Vapreotide reduces splanchnic blood flow; inhibits growth hormone release, and inhibits the release of peptides and vasoactive compounds from neuroendocrine tumors.
Mechanism of actionThe exact mechanism of action is unknown, although one study has provided in vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect in the analgesic effects of vapreotide (PMID: 7556407).
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationVapreotide is 76% eliminated in bile. The remainder is renally eliminated.
Half life30 minutes
ClearanceNot Available
ToxicitySafety data are limited, however, headache, fatigue, diarrhea, nausea, vomiting, and abdominal pain have been reported commonly with the use of vapreotide.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9656
Blood Brain Barrier-0.9221
Caco-2 permeable-0.7899
P-glycoprotein substrateSubstrate0.8572
P-glycoprotein inhibitor INon-inhibitor0.9346
P-glycoprotein inhibitor IINon-inhibitor0.9514
Renal organic cation transporterNon-inhibitor0.8571
CYP450 2C9 substrateNon-substrate0.8172
CYP450 2D6 substrateNon-substrate0.7495
CYP450 3A4 substrateSubstrate0.5808
CYP450 1A2 substrateNon-inhibitor0.8063
CYP450 2C9 inhibitorNon-inhibitor0.638
CYP450 2D6 inhibitorNon-inhibitor0.8286
CYP450 2C19 inhibitorNon-inhibitor0.6249
CYP450 3A4 inhibitorNon-inhibitor0.739
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5526
Ames testNon AMES toxic0.7151
CarcinogenicityNon-carcinogens0.8667
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.7335 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.973
hERG inhibition (predictor II)Inhibitor0.6667
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0103 mg/mLALOGPS
logP3.1ALOGPS
logP8.47ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)2.82ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area376.06 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity320.8 m3·mol-1ChemAxon
Polarizability117.6 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Venkata Raghavendra Palle, Maheedhara Reddy Challa, “PROCESS FOR PREPARING VAPREOTIDE.” U.S. Patent US20070111930, issued May 17, 2007.

US20070111930
General References
  1. Sarr MG: The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. J Am Coll Surg. 2003 Apr;196(4):556-64; discussion 564-5; author reply 565. [PubMed:12691930 ]
  2. Authors unspecified: Vapreotide: BMY 41606, RC 160, Sanvar. Drugs R D. 2003;4(5):326-30. [PubMed:12952505 ]
  3. Norman P: Vapreotide (Debipharm). IDrugs. 2000 Nov;3(11):1358-72. [PubMed:16047258 ]
  4. Betoin F, Ardid D, Herbet A, Aumaitre O, Kemeny JL, Duchene-Marullaz P, Lavarenne J, Eschalier A: Evidence for a central long-lasting antinociceptive effect of vapreotide, an analog of somatostatin, involving an opioidergic mechanism. J Pharmacol Exp Ther. 1994 Apr;269(1):7-14. [PubMed:7909563 ]
  5. Girard PM, Goldschmidt E, Vittecoq D, Massip P, Gastiaburu J, Meyohas MC, Coulaud JP, Schally AV: Vapreotide, a somatostatin analogue, in cryptosporidiosis and other AIDS-related diarrhoeal diseases. AIDS. 1992 Jul;6(7):715-8. [PubMed:1354449 ]
  6. Stiefel F, Morant R: Vapreotide, a new somatostatin analogue in the palliative management of obstructive ileus in advanced cancer. Support Care Cancer. 1993 Jan;1(1):57-8. [PubMed:7511473 ]
  7. Betoin F, Eschalier A, Duchene-Marullaz P, Lavarenne J: Seven-day antinociceptive effect of a sustained release vapreotide formulation. Neuroreport. 1994 Jan 31;5(5):642-4. [PubMed:7912964 ]
External Links
ATC CodesH01CB04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vapreotide.
BevacizumabBevacizumab may increase the cardiotoxic activities of Vapreotide.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vapreotide.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vapreotide.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vapreotide.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vapreotide.
DigoxinDigoxin may decrease the cardiotoxic activities of Vapreotide.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vapreotide.
OuabainOuabain may decrease the cardiotoxic activities of Vapreotide.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vapreotide.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vapreotide.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inducer
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 PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor i...
Gene Name:
SSTR2
Uniprot ID:
P30874
Molecular Weight:
41332.37 Da
References
  1. Fortune BE, Jackson J, Leonard J, Trotter JF: Vapreotide: a somatostatin analog for the treatment of acute variceal bleeding. Expert Opin Pharmacother. 2009 Oct;10(14):2337-42. doi: 10.1517/14656560903207019. [PubMed:19708854 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
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 activity of SSTR2 following heterodimerization.
Gene Name:
SSTR5
Uniprot ID:
P35346
Molecular Weight:
39201.925 Da
References
  1. Fortune BE, Jackson J, Leonard J, Trotter JF: Vapreotide: a somatostatin analog for the treatment of acute variceal bleeding. Expert Opin Pharmacother. 2009 Oct;10(14):2337-42. doi: 10.1517/14656560903207019. [PubMed:19708854 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Tachykinin receptor activity
Specific Function:
This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.
Gene Name:
TACR1
Uniprot ID:
P25103
Molecular Weight:
46250.5 Da
References
  1. Betoin F, Advenier C, Fardin V, Wilcox G, Lavarenne J, Eschalier A: In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin. Eur J Pharmacol. 1995 Jun 12;279(2-3):241-9. [PubMed:7556407 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24