| Primary information |
|---|
| ThPP ID | Th1099 |
| Therapeutic Peptide/Protein Name | Mecasermin |
| Sequence | GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFR view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 7649 |
| Chemical Formula | C331H518N94O101S7 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | 2 hours |
| Description | E. coli derived, recombinant human insulin-like growth factor-1 (rhIGF-1). It has 70 amino acids in a single chain (identical to the endogenous human protein), with three intramolecular disulfide bridges and a molecular weight of 7649 daltons. |
| Indication/Disease | 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. |
| 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. |
| Metabolism | Both the liver and the kidney have been shown to metabolize IGF-1. |
| 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] |
| Clearance | N.A. |
| Categories | N.A. |
| Patents Number | US5681814 |
| Date of Issue | 19/09/01 |
| Date of Expiry | 19/09/21 |
| Drug Interaction | N.A. |
| Target | Insulin-like growth factor 1 receptor,Insulin-like growth factor-binding protein 3,Insulin receptor,Cation-independent mannose-6-phosphate receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | N.A. |
| Company | N.A. |
| Brand Discription | N.A. |
| Prescribed for | N.A. |
| Chemical Name | N.A. |
| Formulation | N.A. |
| Physcial Appearnce | N.A. |
| Route of Administration | N.A. |
| Recommended Dosage | N.A. |
| Contraindication | N.A. |
| Side Effects | N.A. |
| Useful Link | N.A. |
| PubMed ID | 19627167, 19198769 |
| 3-D Structure | Th1099 (View) or (Download) |