Identification

Name
Vapreotide
Accession Number
DB04894
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • Vapreotida
  • Vapreotidum
External IDs
BMY 41606 / BMY-41606 / RC-160
Product Ingredients
IngredientUNIICASInChI Key
Vapreotide acetate5562377HFV849479-74-9KBIZSMHYSQUHDH-UHFFFAOYSA-N
International/Other Brands
Octastatin / Sanvar / Sanvar IR
Categories
UNII
2PK59M9GFF
CAS number
103222-11-3
Weight
Average: 1131.38
Monoisotopic: 1130.48301423
Chemical Formula
C57H70N12O9S2
InChI Key
SWXOGPJRIDTIRL-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][[email protected]@](N)(CC1=CC=CC=C1)C(O)=N[[email protected]@]1([H])CSSC[[email protected]]([H])(N=C(O)[[email protected]@]([H])(N=C(O)[[email protected]]([H])(CCCCN)N=C(O)[[email protected]@]([H])(CC2=CNC3=CC=CC=C23)N=C(O)[[email protected]]([H])(CC2=CC=C(O)C=C2)N=C1O)C(C)C)C(O)=N[[email protected]@]([H])(CC1=CNC2=CC=CC=C12)C(O)=N

Pharmacology

Indication

For 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.

Structured Indications
Not Available
Pharmacodynamics

Vapreotide 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 action

The 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).

TargetActionsOrganism
ASomatostatin receptor type 2
inducer
Human
ASomatostatin receptor type 5
agonist
Human
USubstance-P receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Vapreotide is 76% eliminated in bile. The remainder is renally eliminated.

Half life

30 minutes

Clearance
Not Available
Toxicity

Safety 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vapreotide.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Vapreotide.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Vapreotide.Approved, Investigational
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Vapreotide.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vapreotide.Approved
CodeineThe metabolism of Codeine can be decreased when combined with Vapreotide.Approved, Illicit
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vapreotide.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be decreased when it is combined with Vapreotide.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Vapreotide.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vapreotide.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vapreotide.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Vapreotide.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vapreotide.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Vapreotide.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Vapreotide.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Vapreotide.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Vapreotide.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Vapreotide.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vapreotide.Approved, Vet Approved
PegvisomantThe risk or severity of adverse effects can be increased when Vapreotide is combined with Pegvisomant.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Vapreotide.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Vapreotide.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vapreotide.Approved, Investigational
Food Interactions
Not 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
KEGG Drug
D06281
ChemSpider
5293243
ChEMBL
CHEMBL3349523
Therapeutic Targets Database
DAP001242
PharmGKB
PA164743146
ATC Codes
H01CB04 — Vapreotide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentGastric Varices / Oesophageal haemorrhage / Portal Hypertension / Varices, Esophageal1
3TerminatedSupportive CareMalignant Neoplasm of Pancreas / Perioperative/Postoperative Complications1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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 / Phenylalanine and derivatives / Macrolactams / N-acyl-alpha amino acids and derivatives / Tryptamines and derivatives / Alpha amino acid amides / 3-alkylindoles / Amphetamines and derivatives / 1-hydroxy-2-unsubstituted benzenoids / Aralkylamines
show 13 more
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
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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 ...
Gene Name
SSTR2
Uniprot ID
P30874
Uniprot Name
Somatostatin receptor type 2
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 act...
Gene Name
SSTR5
Uniprot ID
P35346
Uniprot Name
Somatostatin receptor type 5
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 aff...
Gene Name
TACR1
Uniprot ID
P25103
Uniprot Name
Substance-P receptor
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]

Drug created on October 21, 2007 16:23 / Updated on October 02, 2017 05:39