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Identification
NameVapreotide
Accession NumberDB04894
Typesmall molecule
Groupsapproved, investigational
Description

Vapreotide is a synthetic octapeptide somatostatin analog. It was being studied for the treatment of cancer.

Structure
Thumb
Synonyms
SynonymLanguageCode
VapreotidaSpanishINN
VapreotidumLatinINN
Salts
Name/CAS Structure Properties
Vapreotide acetate
Thumb
  • InChI Key: KBIZSMHYSQUHDH-BBPGQOGGSA-N
  • Monoisotopic Mass: 1190.50414265
  • Average Mass: 1191.423
DBSALT000535
Brand names
NameCompany
OctastatinNot Available
SanvarNot Available
Sanvar IRNot Available
Brand mixturesNot Available
Categories
CAS number103222-11-3
WeightAverage: 1131.371
Monoisotopic: 1130.483013278
Chemical FormulaC57H70N12O9S2
InChI KeyInChIKey=GAWXLRUZZFSQON-UHFFFAOYSA-N
InChI
InChI=1S/C57H70N12O9S2/c1-32(2)49-57(78)68-48(55(76)64-44(50(60)71)28-37-26-35-14-6-8-16-41(35)62-37)31-80-79-30-47(67-51(72)40(59)24-33-12-4-3-5-13-33)56(77)65-45(25-34-19-21-38(70)22-20-34)53(74)66-46(27-36-29-61-42-17-9-7-15-39(36)42)54(75)63-43(52(73)69-49)18-10-11-23-58/h3-9,12-17,19-22,26,29,32,40,43-49,61-62,70H,10-11,18,23-25,27-28,30-31,58-59H2,1-2H3,(H2,60,71)(H,63,75)(H,64,76)(H,65,77)(H,66,74)(H,67,72)(H,68,78)(H,69,73)
IUPAC Name
2-amino-N-[10-(4-aminobutyl)-4-{[1-carbamoyl-2-(1H-indol-2-yl)ethyl]carbamoyl}-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-pentaazacycloicosan-19-yl]-3-phenylpropanamide
SMILES
CC(C)C1NC(=O)C(CCCCN)NC(=O)C(CC2=CNC3=C2C=CC=C3)NC(=O)C(CC2=CC=C(O)C=C2)NC(=O)C(CSSCC(NC1=O)C(=O)NC(CC1=CC2=CC=CC=C2N1)C(N)=O)NC(=O)C(N)CC1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentCyclic Peptides
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; Alpha Amino Acid Amides; Phenylpropylamines; Amphetamines and Derivatives; Indoles; Phenols and Derivatives; Substituted Pyrroles; Primary Carboxylic Acid Amides; Secondary Carboxylic Acid Amides; Organic Disulfides; Enolates; Enols; Carboxylic Acids; Polyamines; Monoalkylamines
Substituentsn-acyl-alpha amino acid or derivative; alpha-amino acid amide; amphetamine or derivative; alpha-amino acid or derivative; phenylpropylamine; indole or derivative; indole; phenol derivative; benzene; substituted pyrrole; pyrrole; secondary carboxylic acid amide; carboxamide group; primary carboxylic acid amide; organic disulfide; enolate; carboxylic acid; polyamine; enol; amine; primary amine; organonitrogen compound; primary aliphatic amine
Classification descriptionThis compound belongs to the cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
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).
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
Property Value Probability
Human Intestinal Absorption + 0.9656
Blood Brain Barrier - 0.9221
Caco-2 permeable - 0.7899
P-glycoprotein substrate Substrate 0.8572
P-glycoprotein inhibitor I Non-inhibitor 0.9346
P-glycoprotein inhibitor II Non-inhibitor 0.9514
Renal organic cation transporter Non-inhibitor 0.8571
CYP450 2C9 substrate Non-substrate 0.8172
CYP450 2D6 substrate Non-substrate 0.7495
CYP450 3A4 substrate Substrate 0.5808
CYP450 1A2 substrate Non-inhibitor 0.8063
CYP450 2C9 substrate Non-inhibitor 0.638
CYP450 2D6 substrate Non-inhibitor 0.8286
CYP450 2C19 substrate Non-inhibitor 0.6249
CYP450 3A4 substrate Non-inhibitor 0.739
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5526
Ames test Non AMES toxic 0.7151
Carcinogenicity Non-carcinogens 0.8667
Biodegradation Not ready biodegradable 0.9935
Rat acute toxicity 2.7335 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.973
hERG inhibition (predictor II) Inhibitor 0.6667
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility3.99e-03 g/lALOGPS
logP2.7ALOGPS
logP0.76ChemAxon
logS-5.5ALOGPS
pKa (strongest acidic)9.43ChemAxon
pKa (strongest basic)10.26ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count11ChemAxon
hydrogen donor count13ChemAxon
polar surface area350.64ChemAxon
rotatable bond count18ChemAxon
refractivity306.2ChemAxon
polarizability118.82ChemAxon
number of rings7ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
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 Reference
  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
  2. Vapreotide: BMY 41606, RC 160, Sanvar. Drugs R D. 2003;4(5):326-30. Pubmed
  3. Norman P: Vapreotide (Debipharm). IDrugs. 2000 Nov;3(11):1358-72. Pubmed
  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
  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
  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
  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
External Links
ResourceLink
KEGG DrugD06281
PubChem Compound23725064
PubChem Substance46506923
ChemSpider64425
Therapeutic Targets DatabaseDAP001242
PharmGKBPA164743146
ATC CodesH01CB04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

1. Somatostatin receptor type 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Somatostatin receptor type 2 P30874 Details

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. Pubmed

2. Somatostatin receptor type 5

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Somatostatin receptor type 5 P35346 Details

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. Pubmed

3. Substance-P receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Substance-P receptor P25103 Details

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26