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Identification
NameSomatropin recombinant
Accession NumberDB00052  (BIOD00086, BTD00086)
Typebiotech
Groupsapproved, investigational
Description

Recombinant human growth hormone (somatotropin) 191 residues, MW 22.1 kD, synthesized in E. coli

Protein structureDb00052
Protein chemical formulaC990H1532N262O300S7
Protein average weight22129.0000
Sequences
>DB00052 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
SomatropinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
BioTropinBiotech General
GenotropinPfizer
HumatropeEli Lilly
NorditropinNovo Nordisk
NutropinGenentech Inc.
NutropinAQGenentech Inc.
ProtropinGenentech Inc.
SaizenSerono SA
SerostimSerono SA
Tev-TropinGATE
Brand mixturesNot Available
CategoriesNot Available
CAS number12629-01-5
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
IndicationFor treatment of dwarfism, acromegaly and prevention of HIV-induced weight loss
PharmacodynamicsUsed in the treatment of dwarfism and growth failure, growth hormone (hGH) stimulates skeletal growth in pediatric patients with growth failure due to a lack of adequate secretion of endogenous GH. Skeletal growth is accomplished at the epiphyseal plates at the ends of a growing bone. Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and one of its mediators, IGF-I (insulin-like growth factor).
Mechanism of actionhGH binds to the human growth hormone receptor (GHR). Upon binding, hGH causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 and GHR. These events recruit and/or activate a variety of signaling molecules, including MAP kinases, insulin receptor substrates, phosphatidylinositol 3' phosphate kinase, diacylglycerol, protein kinase C, intracellular calcium, and Stat transcription factors. These signaling molecules contribute to the GH-induced changes in enzymatic activity, transport function, and gene expression that ultimately culminate in changes in growth and metabolism.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationAlthough calcium excretion in the urine is increased, there is a simultaneous increase in calcium absorption from the intestine. Somatropin stimulates the synthesis of chondroitin sulfate and collagen, and increases the urinary excretion of hydroxyproline.
Half lifeNot Available
Clearance
  • 2.3 +/- 1.8 mL/min/kg [GHD patients (IV 33 ng/kg/min)]
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
  • Genentech inc
  • Serono laboratories inc
  • Cangene corp
  • Ferring pharmaceuticals inc
  • Pharmacia and upjohn co
  • Eli lilly and co
  • Novo nordisk inc
  • Sandoz inc
  • Emd serono inc
  • Lg life sciences ltd
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous
Prices
Unit descriptionCostUnit
Humatrope 24 mg cartridge1822.9USDcartridge
Norditropin flexpro 15 mg/1.51179.54USDml
Norditropin 15 mg/1.5ml Solution 1.5ml Cartridge1168.32USDcartridge
Norditropin NordiFlex Pen 15 mg/1.5ml Solution 1 Syringe = 1.5ml1168.32USDpen
Norditropin 15 mg/1.5 ml cartridge1123.38USDml
Norditropin nordiflx 15 mg/1.51123.38USDml
Genotropin 12 mg Solution928.36USDeach
Humatrope 12 mg cartridge911.45USDcartridge
Nutropin 10 mg vial784.7USDvial
Nutropin aq 20 mg/2ml pen cart759.55USDml
Nutropin aq nuspin 20 pen cart759.55USDml
Norditropin NordiFlex Pen 10 mg/1.5ml Solution 1 Syringe = 1.5ml753.86USDpen
Norditropin nordiflex 30 mg/3748.92USDml
Saizen 8.8 mg Solution Vial626.1USDvial
Saizen Click.Easy 8.8 mg Solution Vial626.1USDvial
Saizen 8.8 mg vial602.02USDvial
Protropin 10 mg Solution Vial549.9USDvial
Humatrope 6 mg cartridge455.72USDcartridge
Genotropin MiniQuick 0.8 mg (7 Cartridges Per Box)433.56USDbox
Serostim 8.8 mg vial418.66USDvial
Nutropin 5 mg vial392.35USDvial
Saizen 5 mg Solution Vial391.31USDvial
Genotropin 5.8 mg Cartridge391.21USDcartridge
Norditropin 5 mg/1.5ml Solution 1.5ml Cartridge389.44USDcartridge
Norditropin NordiFlex Pen 5 mg/1.5ml Solution 1 Syringe = 1.5ml389.44USDpen
Saizen 5 mg vial376.26USDvial
Serostim 6 mg vial332.86USDvial
Genotropin MiniQuick 0.6 mg (7 Cartridges Per Box)326.67USDbox
Omnitrope 5.8 mg Solution Vial283.38USDvial
Serostim 5 mg vial277.38USDvial
Protropin 5 mg Solution Vial274.95USDvial
Tev-Tropin 5 mg Solution Vial259.45USDvial
Tev-tropin 5 mg vial239.51USDvial
Genotropin MiniQuick 0.4 mg (7 Cartridges Per Box)228.45USDbox
Serostim 4 mg vial221.9USDvial
Genotropin MiniQuick 2 mg (7 Cartridges Per Box)154.72USDcartridge
Genotropin miniquick 2 mg150.46USDeach
Genotropin miniquick 1.8 mg135.41USDeach
Genotropin MiniQuick 1.6 mg (7 Cartridges Per Box)123.78USDcartridge
Genotropin miniquick 1.6 mg120.37USDeach
Genotropin MiniQuick 0.2 mg (7 Cartridges Per Box)110.52USDbox
Genotropin MiniQuick 1.4 mg (7 Cartridges Per Box)108.78USDcartridge
Genotropin miniquick 1.4 mg105.32USDeach
Genotropin MiniQuick 1.2 mg (7 Cartridges Per Box)92.83USDcartridge
Genotropin miniquick 1.2 mg90.28USDeach
Genotropin MiniQuick 1 mg (7 Cartridges Per Box)77.36USDcartridge
Genotropin miniquick 1 mg75.23USDeach
Genotropin miniquick 0.8 mg60.19USDeach
Genotropin miniquick 0.6 mg45.14USDeach
Genotropin miniquick 0.4 mg30.09USDeach
Genotropin miniquick 0.2 mg15.05USDeach
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Patents
CountryPatent NumberApprovedExpires (estimated)
United States61528971998-11-202018-11-20
United States52887031994-10-072011-10-07
Canada22525352009-06-232017-04-24
Canada13264391994-01-252011-01-25
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 Reference
  1. Seltzer V, Tonge SR: Proceedings: Methylamphetamine withdrawal as a model for the depressive state: antagonism of post-amphetamine depression by imipramine. J Pharm Pharmacol. 1975 Dec;27 Suppl?-2:16P. Pubmed
  2. Alba-Roth J, Muller OA, Schopohl J, von Werder K: Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab. 1988 Dec;67(6):1186-9. Pubmed
  3. Scarth JP: Modulation of the growth hormone-insulin-like growth factor (GH-IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review. Xenobiotica. 2006 Feb-Mar;36(2-3):119-218. Pubmed
  4. Takahashi Y, Kipnis DM, Daughaday WH: Growth hormone secretion during sleep. J Clin Invest. 1968 Sep;47(9):2079-90. Pubmed
External Links
ResourceLink
UniProtP58756
GenbankAF374232
PharmGKBPA451446
Drug Product Database2243079
RxListhttp://www.rxlist.com/cgi/generic3/nutropin.htm
Drugs.comhttp://www.drugs.com/cdi/somatropin-rdna-origin-nonrefrigerated.html
WikipediaSomatropin_recombinant
ATC CodesH01AC01
AHFS CodesNot Available
PDB Entries
FDA labelshow(241 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcarboseSomatropin may antagonize the hypoglycemic effect of acarbose. Monitor for changes in fasting and postprandial blood sugars.
ChlorpropamideSomatropin may antagonize the hypoglycemic effect of chlorpropamide. Monitor for changes in fasting and postprandial blood sugars.
ExenatideSomatropin may antagonize the hypoglycemic effect of exenatide. Monitor for changes in fasting and postprandial blood sugars.
GliclazideSomatropin may antagonize the hypoglycemic effect of gliclazide. Monitor for changes in fasting and postprandial blood sugars.
GlimepirideSomatropin may antagonize the hypoglycemic effect of glimepiride. Monitor for changes in fasting and postprandial blood sugars.
GlipizideSomatropin may antagonize the hypoglycemic effect of glipizide. Monitor for changes in fasting and postprandial blood sugars.
GlyburideSomatropin may antagonize the hypoglycemic effect of glibenclamide. Monitor for changes in fasting and postprandial blood sugars.
Insulin AspartSomatropin may antagonize the hypoglycemic effect of insulin aspart. Monitor for changes in fasting and postprandial blood sugars.
Insulin DetemirSomatropin may antagonize the hypoglycemic effect of insulin detemir. Monitor for changes in fasting and postprandial blood sugars.
Insulin GlargineSomatropin may antagonize the hypoglycemic effect of insulin glargine. Monitor for changes in fasting and postprandial blood sugars.
Insulin GlulisineSomatropin may antagonize the hypoglycemic effect of insulin glulisine. Monitor for changes in fasting and postprandial blood sugars.
LiraglutideSomatropin may antagonize the hypoglycemic effect of liraglutide. Monitor for changes in fasting and postprandial blood sugars.
MetforminSomatropin may antagonize the hypoglycemic effect of metformin. Monitor for changes in fasting and postprandial blood sugars.
MiglitolSomatropin may antagonize the hypoglycemic effect of miglitol. Monitor for changes in fasting and postprandial blood sugars.
NateglinideSomatropin may antagonize the hypoglycemic effect of nateglinide. Monitor for changes in fasting and postprandial blood sugars.
PioglitazoneSomatropin may antagonize the hypoglycemic effect of pioglitazone. Monitor for changes in fasting and postprandial blood sugars.
RosiglitazoneSomatropin may antagonize the hypoglycemic effect of rosiglitazone. Monitor for changes in fasting and postprandial blood sugars.
SaxagliptinSomatropin may antagonize the hypoglycemic effect of saxagliptin. Monitor for changes in fasting and postprandial blood sugars.
SitagliptinSomatropin may antagonize the hypoglycemic effect of sitagliptin. Monitor for changes in fasting and postprandial blood sugars.
TolazamideSomatropin may antagonize the hypoglycemic effect of Tolazamide. Dose adjustments of Tolazamide may be required.
TolbutamideSomatropin may antagonize the hypoglycemic effect of Tolbutamide. Dose adjustments of Tolbutamide may be required.
Food InteractionsNot Available

1. Growth hormone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details
Growth hormone receptor P10912 Details

References:

  1. Walenkamp MJ, Wit JM: Genetic disorders in the growth hormone – insulin-like growth factor-I axis. Horm Res. 2006;66(5):221-30. Pubmed
  2. Wu XY, Xu Z, Chen C, Liu FK, Li JS: [Correlation of growth hormone receptor expression to preoperative radiosensitivity of rectal cancer patients] Ai Zheng. 2006 Sep;25(9):1162-7. Pubmed
  3. Adriani M, Garbi C, Amodio G, Russo I, Giovannini M, Amorosi S, Matrecano E, Cosentini E, Candotti F, Pignata C: Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus. J Immunol. 2006 Nov 15;177(10):6889-95. Pubmed
  4. Choi JH, Kim HS, Kim SH, Yang YR, Bae YS, Chang JS, Kwon HM, Ryu SH, Suh PG: Phospholipase Cgamma1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B. Nat Cell Biol. 2006 Dec;8(12):1389-97. Epub 2006 Nov 26. Pubmed
  5. Bernstein RM, Leigh SR, Donovan SM, Monaco MH: Hormones and body size evolution in papionin primates. Am J Phys Anthropol. 2007 Feb;132(2):247-60. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prolactin receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Prolactin receptor P16471 Details

References:

  1. Keeler C, Jablonski EM, Albert YB, Taylor BD, Myszka DG, Clevenger CV, Hodsdon ME: The kinetics of binding human prolactin, but not growth hormone, to the prolactin receptor vary over a physiologic pH range. Biochemistry. 2007 Mar 6;46(9):2398-410. Epub 2007 Feb 6. Pubmed
  2. Ahmed TA, Buzzelli MD, Lang CH, Capen JB, Shumate ML, Navaratnarajah M, Nagarajan M, Cooney RN: Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes. Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1793-803. Epub 2007 Mar 29. Pubmed
  3. Moderscheim TA, Gorba T, Pathipati P, Kokay IC, Grattan DR, Williams CE, Scheepens A: Prolactin is involved in glial responses following a focal injury to the juvenile rat brain. Neuroscience. 2007 Mar 30;145(3):963-73. Epub 2007 Feb 20. Pubmed
  4. Cunningham BC, Bass S, Fuh G, Wells JA: Zinc mediation of the binding of human growth hormone to the human prolactin receptor. Science. 1990 Dec 21;250(4988):1709-12. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 13, 2013 10:48