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Identification
NamePegvisomant
Accession NumberDB00082  (BTD00044, BIOD00044)
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
Related Articles
Protein chemical formulaC990H1532N262O300S7
Protein average weight22129.0 Da
Sequences
>DB00082 sequence
FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPT
PSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEG
IQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIV
QCRSVEGSCGF
Download FASTA Format
Synonyms
GH
GH-N
Growth hormone
Growth hormone 1
Pituitary growth hormone
Somatotropin precursor
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Somavertkit; powder for solution25 mgsubcutaneousPfizer Canada Inc2016-03-10Not applicableCanada
Somavertkit; powder for solution10 mgsubcutaneousPfizer Canada Inc2006-01-24Not applicableCanada
SomavertkitPharmacia And Upjohn Company Llc2014-07-312016-04-23Us
SomavertkitPharmacia And Upjohn Company Llc2014-07-312016-04-23Us
SomavertkitPharmacia And Upjohn Company Llc2003-05-252016-04-23Us
SomavertkitPharmacia And Upjohn Company Llc2003-05-252016-04-23Us
SomavertkitPharmacia And Upjohn Company Llc2003-05-252016-04-23Us
Somavertkit; powder for solution20 mgsubcutaneousPfizer Canada Inc2006-01-24Not applicableCanada
Somavertkit; powder for solution30 mgsubcutaneousPfizer Canada Inc2016-03-10Not applicableCanada
Somavertkit; powder for solution15 mgsubcutaneousPfizer Canada Inc2006-01-24Not applicableCanada
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIN824AOU5XV
CAS number218620-50-9
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 7 L
Protein bindingNot Available
MetabolismNot Available
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
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers
Dosage forms
FormRouteStrength
Kit
Kit; powder for solutionsubcutaneous10 mg
Kit; powder for solutionsubcutaneous15 mg
Kit; powder for solutionsubcutaneous20 mg
Kit; powder for solutionsubcutaneous25 mg
Kit; powder for solutionsubcutaneous30 mg
Prices
Unit descriptionCostUnit
Somavert 20 mg vial208.38USD vial
Somavert 15 mg vial156.29USD vial
Somavert 10 mg vial104.18USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2102129 No2003-04-012012-05-01Canada
CA2230492 No2009-05-262016-09-20Canada
US5350836 No1994-09-272011-09-27Us
US5849535 No1997-03-252017-03-25Us
US6057292 No1995-09-212015-09-21Us
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
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 ReferencesNot Available
External Links
ATC CodesH01AX01
AHFS Codes
  • 68:30.08
PDB Entries
FDA labelDownload (864 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcarbosePegvisomant may increase the hypoglycemic activities of Acarbose.
AlbiglutidePegvisomant may increase the hypoglycemic activities of Albiglutide.
AlfentanilThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Alfentanil.
AlogliptinPegvisomant may increase the hypoglycemic activities of Alogliptin.
BromocriptinePegvisomant may increase the hypoglycemic activities of Bromocriptine.
BuprenorphineThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Buprenorphine.
ButorphanolThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Butorphanol.
ChlorpropamidePegvisomant may increase the hypoglycemic activities of Chlorpropamide.
DapagliflozinPegvisomant may increase the hypoglycemic activities of Dapagliflozin.
DisopyramidePegvisomant may increase the hypoglycemic activities of Disopyramide.
DulaglutidePegvisomant may increase the hypoglycemic activities of Dulaglutide.
EmpagliflozinPegvisomant may increase the hypoglycemic activities of Empagliflozin.
ExenatidePegvisomant may increase the hypoglycemic activities of Exenatide.
FentanylThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Fentanyl.
GliclazidePegvisomant may increase the hypoglycemic activities of Gliclazide.
GlimepiridePegvisomant may increase the hypoglycemic activities of Glimepiride.
GlipizidePegvisomant may increase the hypoglycemic activities of Glipizide.
GlyburidePegvisomant may increase the hypoglycemic activities of Glyburide.
HydrocodoneThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Hydrocodone.
HydromorphoneThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Hydromorphone.
Insulin AspartPegvisomant may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecPegvisomant may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirPegvisomant may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlarginePegvisomant may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisinePegvisomant may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanPegvisomant may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproPegvisomant may increase the hypoglycemic activities of Insulin Lispro.
LanreotideThe risk or severity of adverse effects can be increased when Lanreotide is combined with Pegvisomant.
LevorphanolThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Levorphanol.
LiraglutidePegvisomant may increase the hypoglycemic activities of Liraglutide.
MecaserminPegvisomant may increase the hypoglycemic activities of Mecasermin.
MetforminPegvisomant may increase the hypoglycemic activities of Metformin.
MethadoneThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Methadone.
MifepristonePegvisomant may increase the hypoglycemic activities of Mifepristone.
MiglitolPegvisomant may increase the hypoglycemic activities of Miglitol.
MorphineThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Morphine.
NalbuphineThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Nalbuphine.
NateglinidePegvisomant may increase the hypoglycemic activities of Nateglinide.
OctreotideThe risk or severity of adverse effects can be increased when Octreotide is combined with Pegvisomant.
OxycodoneThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Oxycodone.
OxymorphoneThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Oxymorphone.
PasireotideThe risk or severity of adverse effects can be increased when Pasireotide is combined with Pegvisomant.
PegloticaseThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Pegloticase.
PentamidinePegvisomant may increase the hypoglycemic activities of Pentamidine.
PentazocineThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Pentazocine.
PethidineThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Pethidine.
PioglitazonePegvisomant may increase the hypoglycemic activities of Pioglitazone.
PramlintidePegvisomant may increase the hypoglycemic activities of Pramlintide.
QuininePegvisomant may increase the hypoglycemic activities of Quinine.
RemifentanilThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Remifentanil.
RepaglinidePegvisomant may increase the hypoglycemic activities of Repaglinide.
RosiglitazonePegvisomant may increase the hypoglycemic activities of Rosiglitazone.
SaxagliptinPegvisomant may increase the hypoglycemic activities of Saxagliptin.
SitagliptinPegvisomant may increase the hypoglycemic activities of Sitagliptin.
SufentanilThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Sufentanil.
SulfadiazinePegvisomant may increase the hypoglycemic activities of Sulfadiazine.
SunitinibPegvisomant may increase the hypoglycemic activities of Sunitinib.
TapentadolThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Tapentadol.
TolazamidePegvisomant may increase the hypoglycemic activities of Tolazamide.
TolbutamidePegvisomant may increase the hypoglycemic activities of Tolbutamide.
TramadolThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Tramadol.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Protein kinase binding
Specific Function:
Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
Gene Name:
GHR
Uniprot ID:
P10912
Molecular Weight:
71498.885 Da
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. doi: 10.1210/jc.2009-0381. Epub 2009 Oct 9. [PubMed:19820031 ]
  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:17322491 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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 Oct;33(9):663-70. doi: 10.3275/7143. Epub 2010 Jul 1. [PubMed:20595800 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
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.
Gene Name:
CYP27A1
Uniprot ID:
Q02318
Molecular Weight:
60234.28 Da
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:12597773 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Manganese ion binding
Specific Function:
This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.
Gene Name:
GLUL
Uniprot ID:
P15104
Molecular Weight:
42064.15 Da
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:1970314 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular Weight:
55710.075 Da
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. doi: 10.1124/dmd.109.026963. Epub 2009 Apr 1. [PubMed:19339376 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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:9661620 ]
  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:16291874 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
References
  1. Lamartiniere CA: Growth hormone modulates serum cholinesterase. Endocrinology. 1986 Mar;118(3):1252-4. [PubMed:3948777 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
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. doi: 10.1124/dmd.109.026963. Epub 2009 Apr 1. [PubMed:19339376 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Leukotriene-b4 20-monooxygenase activity
Specific Function:
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).
Gene Name:
CYP4A11
Uniprot ID:
Q02928
Molecular Weight:
59347.31 Da
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. doi: 10.1074/jbc.M902074200. Epub 2009 Apr 14. [PubMed:19366684 ]
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Drug created on June 13, 2005 07:24 / Updated on April 28, 2016 02:28