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Identification
NamePegvisomant
Accession NumberDB00082  (BIOD00044, BTD00044)
Typebiotech
Groupsapproved
Description

Pegvisomant is a highly selective growth hormone (GH) receptor antagonist. It is used to treat acromegaly. Unlike dopamine or somatostatin analogs (which inhibit growth hormone secretion), this drug actually blocks the hepatic (GH-mediated) production of insulin like growth factor (IGF-1), which is the main mediator of growth hormone activity.

Protein structureDb00082
Protein chemical formulaC990H1532N262O300S7
Protein average weight22129.0000
Sequences
>DB00082 sequence
FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPT
PSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEG
IQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIV
QCRSVEGSCGF
Download FASTA Format
Synonyms
SynonymLanguageCode
GHNot AvailableNot Available
GH-NNot AvailableNot Available
Growth hormoneNot AvailableNot Available
Growth hormone 1Not AvailableNot Available
Pituitary growth hormoneNot AvailableNot Available
Somatotropin precursorNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
SomavertPfizer Inc
Brand mixturesNot Available
CategoriesNot Available
CAS number218620-50-9
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationPegvisomant is a growth hormone receptor antagonist used for the treatment of acromegaly.
PharmacodynamicsSomavert is used for the treatment of acromegaly, which arises from excessive IGF-1 levels. Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH, and thus interferes with GH signal transduction. Inhibition of GH action results in decreased serum concentrations of insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3). This reduces the symptoms of acromegaly.
Mechanism of actionSomavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH. This leads to the normalization of serum IGF-1 levels.
AbsorptionNot Available
Volume of distribution
  • 7 L
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life~6 days
Clearance
  • 36 – 28 mL/h [SC doses ranging from 10 to 20 mg/day]
ToxicityNot Available
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 Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionSubcutaneous
Prices
Unit descriptionCostUnit
Somavert 20 mg vial208.38USDvial
Somavert 15 mg vial156.29USDvial
Somavert 10 mg vial104.18USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States58495351997-03-252017-03-25
United States53508361994-09-272011-09-27
Canada22304922009-05-262016-09-20
Canada21021292003-04-012012-05-01
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point76 °C at pH 3.5Gomez-Orellana, I. et al., Protein Sci. 7:1352-1358 (1998)
hydrophobicity-0.411Not Available
isoelectric point5.27Not Available
Spectra
SpectraNot Available
References
Synthesis Reference

Mandayam J. Narasimhan, John A. Anderson, “Process for the large scale production of human growth hormone by serial secondary suspension culture.” U.S. Patent US4124448, issued January, 1963.

US4124448
General ReferenceNot Available
External Links
ResourceLink
UniProtP58756
GenbankAF374232
PharmGKBPA164749630
Drug Product Database2272199
RxListhttp://www.rxlist.com/cgi/generic3/somavert.htm
Drugs.comhttp://www.drugs.com/cdi/pegvisomant.html
ATC CodesH01AX01
AHFS Codes
  • 68:30.08
PDB Entries
FDA labelshow(864 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
DihydrocodeineOpioids may diminish the therapeutic effect of pegvisomant. It is recommended to monitor therapy.
Food InteractionsNot Available

1. Growth hormone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Growth hormone receptor P10912 Details

References:

  1. Moller L, Norrelund H, Jessen N, Flyvbjerg A, Pedersen SB, Gaylinn BD, Liu J, Thorner MO, Moller N, Lunde Jorgensen JO: Impact of growth hormone receptor blockade on substrate metabolism during fasting in healthy subjects. J Clin Endocrinol Metab. 2009 Nov;94(11):4524-32. Epub 2009 Oct 9. Pubmed
  2. Paisley AN, Hayden K, Ellis A, Anderson J, Wieringa G, Trainer PJ: Pegvisomant interference in GH assays results in underestimation of GH levels. Eur J Endocrinol. 2007 Mar;156(3):315-9. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  4. De Martino MC, Auriemma RS, Brevetti G, Vitale G, Schiano V, Galdiero M, Grasso L, Lombardi G, Colao A, Pivonello R: THE TREATMENT WITH GROWTH HORMONE RECEPTOR ANTAGONIST IN ACROMEGALY: EFFECT ON VASCULAR STRUCTURE AND FUNCTION IN PATIENTS RESISTANT TO SOMATOSTATIN ANALOGUES. J Endocrinol Invest. 2010 Jul 1. Pubmed

1. Sterol 26-hydroxylase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Sterol 26-hydroxylase, mitochondrial Q02318 Details

References:

  1. Araya Z, Tang W, Wikvall K: Hormonal regulation of the human sterol 27-hydroxylase gene CYP27A1. Biochem J. 2003 Jun 1;372(Pt 2):529-34. Pubmed

2. Glutamine synthetase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Glutamine synthetase P15104 Details

References:

  1. Nolan EM, Masters JN, Dunn A: Growth hormone regulation of hepatic glutamine synthetase mRNA levels in rats. Mol Cell Endocrinol. 1990 Mar 5;69(2-3):101-10. Pubmed

3. Cytochrome P450 2C18

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C18 P33260 Details

References:

  1. Lofgren S, Baldwin RM, Carleros M, Terelius Y, Fransson-Steen R, Mwinyi J, Waxman DJ, Ingelman-Sundberg M: Regulation of human CYP2C18 and CYP2C19 in transgenic mice: influence of castration, testosterone, and growth hormone. Drug Metab Dispos. 2009 Jul;37(7):1505-12. Epub 2009 Apr 1. Pubmed

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Liddle C, Goodwin BJ, George J, Tapner M, Farrell GC: Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab. 1998 Jul;83(7):2411-6. Pubmed
  2. Cheung C, Yu AM, Chen CS, Krausz KW, Byrd LG, Feigenbaum L, Edwards RJ, Waxman DJ, Gonzalez FJ: Growth hormone determines sexual dimorphism of hepatic cytochrome P450 3A4 expression in transgenic mice. J Pharmacol Exp Ther. 2006 Mar;316(3):1328-34. Epub 2005 Nov 16. Pubmed

5. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. Lamartiniere CA: Growth hormone modulates serum cholinesterase. Endocrinology. 1986 Mar;118(3):1252-4. Pubmed

6. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Lofgren S, Baldwin RM, Carleros M, Terelius Y, Fransson-Steen R, Mwinyi J, Waxman DJ, Ingelman-Sundberg M: Regulation of human CYP2C18 and CYP2C19 in transgenic mice: influence of castration, testosterone, and growth hormone. Drug Metab Dispos. 2009 Jul;37(7):1505-12. Epub 2009 Apr 1. Pubmed

7. Cytochrome P450 4A11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 4A11 Q02928 Details

References:

  1. Savas U, Machemer DE, Hsu MH, Gaynor P, Lasker JM, Tukey RH, Johnson EF: Opposing roles of peroxisome proliferator-activated receptor alpha and growth hormone in the regulation of CYP4A11 expression in a transgenic mouse model. J Biol Chem. 2009 Jun 12;284(24):16541-52. Epub 2009 Apr 14. Pubmed]

Comments
Drug created on June 13, 2005 07:24 / Updated on September 13, 2013 10:49