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Identification
Name Mecasermin
Accession Number DB01277
Type biotech
Groups approved
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 structure No_structure_small
Protein chemical formula C331H518N94O101S7
Protein average weight 7649.0000
Sequences 
>Mecasermin
GPEILCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMY
CAPLKPAKSA

FASTA
Synonyms
Mecasermin rinfabate
Salts Not Available
Brand names
Name Company
Increlex
Increlex (Tercica)
Iplex
Brand mixtures Not Available
Categories Not Available
CAS number 68562-41-4
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For 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.
Pharmacodynamics Mecasermin 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 action Mecasermin 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.
Absorption While 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 binding In 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 elimination Both the liver and the kidney have been shown to metabolize IGF-1.
Half life 2 hours
Clearance Not Available
Toxicity There 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Tercica inc
  • Insmed inc
Packagers
Dosage forms
Form Route Strength
Solution Subcutaneous
Prices
Unit description Cost Unit
Increlex 40 mg/4 ml vial 232.8 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5681814 1997-09-18 2017-09-18
United States 5200509 1993-04-06 2010-04-06
Properties
State liquid
Experimental Properties Not Available
References
Synthesis Reference Not 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
Resource Link
PharmGKB PA164774876 Link_out
RxList http://www.rxlist.com/cgi/generic/increlex.htm Link_out
Drugs.com http://www.drugs.com/cdi/mecasermin.html Link_out
ATC Codes
  • H01AC03
AHFS Codes Not Available
PDB Entries
FDA label show (490 KB)
MSDS Not Available
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Insulin-like growth factor 1 receptor

Pharmacological action: yes
Actions: agonist

This receptor binds insulin-like growth factor 1 (IGF1) with a high affinity and IGF2 with a lower affinity. It has a tyrosine-protein kinase activity, which is necessary for the activation of the IGF1-stimulated downstream signaling cascade

Organism class: human
UniProt ID: P08069 Link_out
Gene: IGF1R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors

Organism class: human
UniProt ID: P17936 Link_out
Gene: IGFBP3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

This receptor binds insulin and has a tyrosine-protein kinase activity. Isoform Short has a higher affinity for insulin. Mediates the metabolic functions of insulin. Binding to insulin stimulates association of the receptor with downstream mediators including IRS1 and phosphatidylinositol 3'-kinase (PI3K). Can activate PI3K either directly by binding to the p85 regulatory subunit, or indirectly via IRS1

Organism class: human
UniProt ID: P06213 Link_out
Gene: INSR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6- phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2

Organism class: human
UniProt ID: P11717 Link_out
Gene: IGF2R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on May 16, 2007 14:46 / Updated on August 11, 2011 11:11