Banner
Identification
Name Pegvisomant
Accession Number DB00082 (BIOD00044, BTD00044)
Type biotech
Groups approved
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 structure Db00082
Display: 3D Structure
Protein chemical formula C990H1532N262O300S7
Protein average weight 22129.0000
Sequences 
>DB00082 sequence
FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPT
PSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEG
IQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIV
QCRSVEGSCGF

FASTA
Synonyms
GH
GH-N
Growth hormone
Growth hormone 1
Pituitary growth hormone
Somatotropin precursor
Salts Not Available
Brand names
Name Company
Somavert (Pfizer Inc)
Brand mixtures Not Available
Categories
  • Anabolic Agents
  • Hormone Replacement Agents
CAS number 218620-50-9
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Pegvisomant is a growth hormone receptor antagonist used for the treatment of acromegaly.
Pharmacodynamics Somavert 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 action Somavert 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.
Absorption Not Available
Volume of distribution
  • 7 L
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life ~6 days
Clearance
  • 36 – 28 mL/h [SC doses ranging from 10 to 20 mg/day]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers
Dosage forms
Form Route Strength
Powder, for solution Subcutaneous
Prices
Unit description Cost Unit
Somavert 20 mg vial 208.38 USD vial
Somavert 15 mg vial 156.29 USD vial
Somavert 10 mg vial 104.18 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5849535 1997-03-25 2017-03-25
United States 5350836 1994-09-27 2011-09-27
Canada 2230492 2009-05-26 2016-09-20
Canada 2102129 2003-04-01 2012-05-01
Properties
State liquid
Experimental Properties
Property Value Source
melting point 76 °C at pH 3.5 Gomez-Orellana, I. et al., Protein Sci. 7:1352-1358 (1998)
hydrophobicity -0.411 Not Available
isoelectric point 5.27 Not Available
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
UniProt P58756 Link_out
Genbank AF374232 Link_out
PharmGKB PA164749630 Link_out
Drug Product Database 2272199 Link_out
RxList http://www.rxlist.com/cgi/generic3/somavert.htm Link_out
Drugs.com http://www.drugs.com/cdi/pegvisomant.html Link_out
ATC Codes
  • H01AX01
AHFS Codes
  • 68:30.08
PDB Entries
FDA label show (864 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Growth hormone receptor

Pharmacological action: yes
Actions: antagonist

Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling

Organism class: human
UniProt ID: P10912 Link_out
Gene: GHR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 27, mitochondrial

Actions: inducer

Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta- cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3- 25-hydroxylase activity

UniProt ID: Q02318 Link_out
Gene: CYP27A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

ATP + L-glutamate + NH(3) = ADP + phosphate + L-glutamine

UniProt ID: P15104 Link_out
Gene: GLUL Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P33260 Link_out
Gene: CYP2C18 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

An acylcholine + H(2)O = choline + a carboxylate

UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity towards prostaglandins A1 and E1

UniProt ID: Q02928 Link_out
Gene: CYP4A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 July 05, 2012 00:46