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Identification
NameMecasermin
Accession NumberDB01277
Typebiotech
Groupsapproved, investigational
Description

Mecasermin contains recombinant-DNA-engineered human insulin-like growth factor-1 (rhIGF-1). IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 daltons. The amino acid sequence of the product is identical to that of endogenous human IGF-1. The rhIGF-1 protein is synthesized in bacteria (E. coli) that have been modified by the addition of the gene for human IGF-1.

Protein structureDb01277
Protein chemical formulaC331H518N94O101S7
Protein average weight7649.0000
Sequences
>Mecasermin
GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMY
CAPLKPAKSA
Download FASTA Format
Synonyms
SynonymLanguageCode
IGF-1Not AvailableNot Available
IGF1Not AvailableNot Available
Insulin-like growth factor 1Not AvailableNot Available
Mecasermin rinfabateNot AvailableNot Available
Mechano growth factorNot AvailableNot Available
Somatomedin-CNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
IncrelexTercica
IplexNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number68562-41-4
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 the long-term treatment of growth failure in pediatric patients with Primary IGFD or with GH gene deletion who have developed neutralizing antibodies to GH. It is not indicated to treat Secondary IGFD resulting from GH deficiency, malnutrition, hypothyroidism or other causes; it is not a substitute for GH therapy.
PharmacodynamicsMecasermin is a biosynthetic (recombinant DNA origin) form of human insulin growth factor 1 (IGF-1) designed to replace natural IGF-1 in pediatric patients who are deficient, promoting normalized statural growth. Growth hormones (GH) bind to growth hormone receptors (GHR) in the liver and other tissues, which stimulates the synthesis of IGF-1. In target tissues, IGF-1 activates the IGF-1 receptor, resulting in intracellular signals that stimulate growth. Although many actions of the GH are mediated through IGF-1, the precise roles of GH and IGF-1 have not been fully elucidated. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the GH pathway used to promote IGF-1 release (possible GH pathway disruptions include mutations in the GHR, post-GHR signaling pathway, and IGF-1 gene defects).
Mechanism of actionMecasermin supplies recombinant-DNA-origin IGF-1, which binds to the Type I IGF-1 receptor. This receptor exerts intra-cellular signaling activity in a number of processes involved in statural growth, including mitogenesis in multiple tissue types, chondrocyte growth and division along cartilage growth plates, and increases in organ growth.
AbsorptionWhile the bioavailability of rhIGF-1 after subcutaneous administration in healthy subjects has been reported to be close to 100%, the absolute bioavailability of mecasermin given subcutaneously to subjects with primary insulin-like growth factor-1 deficiency (Primary IGFD) has not been determined.
Volume of distribution
  • 0.257 ± 0.073 L/kg [subjects with severe Primary IGFD]
Protein bindingIn blood, IGF-1 is bound to six IGF binding proteins, with > 80% bound as a complex with IGFBP-3 and an acid-labile subunit.
Metabolism

Both the liver and the kidney have been shown to metabolize IGF-1.

Route of eliminationBoth the liver and the kidney have been shown to metabolize IGF-1.
Half life2 hours
ClearanceNot Available
ToxicityThere is no clinical experience with overdosage of mecasermin. Based on known pharmacological effects, acute overdosage would be predicted to lead to hypoglycemia. Long-term overdosage may result in signs and symptoms of acromegaly.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Tercica inc
  • Insmed inc
Packagers
Dosage forms
FormRouteStrength
SolutionSubcutaneous
Prices
Unit descriptionCostUnit
Increlex 40 mg/4 ml vial232.8USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States56818141997-09-182017-09-18
United States52005091993-04-062010-04-06
Properties
Stateliquid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Keating GM: Mecasermin. BioDrugs. 2008;22(3):177-88. Pubmed
  2. Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. Pubmed
  3. Kemp SF: Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options. BioDrugs. 2009;23(3):155-63. doi: 10.2165/00063030-200923030-00002. Pubmed
  4. Rosenbloom AL: Is there a role for recombinant insulin-like growth factor-I in the treatment of idiopathic short stature? Lancet. 2006 Aug 12;368(9535):612-6. Pubmed
  5. Lewis ME, Neff NT, Contreras PC, Stong DB, Oppenheim RW, Grebow PE, Vaught JL: Insulin-like growth factor-I: potential for treatment of motor neuronal disorders. Exp Neurol. 1993 Nov;124(1):73-88. Pubmed
External Links
ResourceLink
PharmGKBPA164774876
RxListhttp://www.rxlist.com/cgi/generic/increlex.htm
Drugs.comhttp://www.drugs.com/cdi/mecasermin.html
ATC CodesH01AC03
AHFS CodesNot Available
PDB Entries
FDA labelshow(490 KB)
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Insulin-like growth factor 1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Insulin-like growth factor 1 receptor P08069 Details

References:

  1. Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. Pubmed

2. Insulin-like growth factor-binding protein 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Insulin-like growth factor-binding protein 3 P17936 Details

References:

  1. Kemp SF: Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options. BioDrugs. 2009;23(3):155-63. Pubmed
  2. Williams RM, McDonald A, O’Savage M, Dunger DB: Mecasermin rinfabate: rhIGF-I/rhIGFBP-3 complex: iPLEX. Expert Opin Drug Metab Toxicol. 2008 Mar;4(3):311-24. Pubmed
  3. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R D. 2005;6(2):120-7. Pubmed

3. Insulin receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Insulin receptor P06213 Details

References:

  1. Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. Pubmed

4. Cation-independent mannose-6-phosphate receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cation-independent mannose-6-phosphate receptor P11717 Details

References:

  1. Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. Pubmed

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Drug created on May 16, 2007 14:46 / Updated on August 07, 2014 11:36