DT-Web

DB01277 - Mecasermin


Identification
Name Mecasermin
Accession Number DB01277
Type biotech
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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 7649.0000
Groups approved
Monoisotopic Weight 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.
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.
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.
Biotransformation 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.
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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Insulin-like growth factor 1 receptor
Name Insulin-like growth factor 1 receptor
Gene Name IGF1R
Pharmacological action yes
Actions agonist
References
  • Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. - Pubmed
DTHybrid score 1.2592
Insulin-like growth factor-binding protein 3
Name Insulin-like growth factor-binding protein 3
Gene Name IGFBP3
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
DTHybrid score 0.8125
Insulin receptor
Name Insulin receptor
Gene Name INSR
Pharmacological action unknown
Actions Not Available
References
  • Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. - Pubmed
DTHybrid score 1.2626
Cation-independent mannose-6-phosphate receptor
Name Cation-independent mannose-6-phosphate receptor
Gene Name IGF2R
Pharmacological action unknown
Actions Not Available
References
  • Rosenbloom AL: Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009 Jan;26(1):40-54. Epub 2009 Jan 28. - Pubmed
DTHybrid score 0.9642

Predictions


Id Partner name Gene Name Score
2503 Phosphomannomutase/phosphoglucomutase algC 0.256
4200 Cytochrome P450 1A2 CYP1A2 0.2384
1372 Insulin receptor substrate 1 IRS1 0.0833
3849 Insulin-like growth factor-binding protein 7 IGFBP7 0.0702
3847 Neuroendocrine convertase 2 PCSK2 0.0702
2009 Protein NOV homolog NOV 0.0702
1949 Carboxypeptidase E CPE 0.0702
3850 Synaptotagmin-like protein 4 SYTL4 0.0702
3848 Neuroendocrine convertase 1 PCSK1 0.0702
3846 Retinoblastoma-associated protein RB1 0.0701
1243 Cathepsin D CTSD 0.0632
2155 Insulin-degrading enzyme IDE 0.0624
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.0595
1176 Mitogen-activated protein kinase 1 MAPK1 0.0487
3844 HLA class II histocompatibility antigen, DQ(6) alpha chain HLA-DQA2 0.0388
587 Serum albumin ALB 0.0297
2299 UDP-N-acetylmuramate--L-alanine ligase murC 0.0205
5312 Kinesin-like protein KIF1A KIF1A 0.0205
2615 Chemotaxis protein cheA cheA 0.0194
2817 Phosphoribosylglycinamide formyltransferase 2 purT 0.0179
2621 Thermoresistant gluconokinase gntK 0.0168
5466 Putative sugar kinase STM4066 0.0167
4517 Probable butyrate kinase 2 buk2 0.0167
2878 Probable serine/threonine-protein kinase pknB pknB 0.0167
4878 Glycoprotein hormones alpha chain CGA 0.0152
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0152
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0152
1072 Granzyme B GZMB 0.0152
4877 Beta-mannanase man 0.0152
4880 Membrane cofactor protein CD46 0.0152
4869 Major capsid protein A430L 0.0152
4852 Reticulon-4 receptor RTN4R 0.0151
4850 Beta-2-glycoprotein 1 APOH 0.0151
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0151
4856 CD209 antigen CD209 0.0151
4845 ADAM 33 ADAM33 0.0151
757 Fusion glycoprotein F0 F 0.0151
4875 Fusion glycoprotein F0 F 0.0151
4889 Ig epsilon chain C region IGHE 0.0151
4189 Alpha-galactosidase A GLA 0.0151
442 Envelope glycoprotein gp41 0.0151
4859 Envelope glycoprotein env 0.0151
4721 Beta-1,4-mannanase manA 0.0151
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0151
1354 Beta-glucuronidase GUSB 0.0151
3352 Structural polyprotein Not Available 0.0151
3628 Structural polyprotein Not Available 0.0151
4892 Structural polyprotein Not Available 0.0151
3669 Ribokinase rbsK 0.0146
2717 Folylpolyglutamate synthase fgs 0.0139
6390 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 ATP2A1 0.0139
1184 Interferon beta IFNB1 0.0132
6858 Inactive carboxylesterase 4 CES1P1 0.0132
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0132
1379 Interleukin-12 subunit beta IL12B 0.0132
793 T-cell surface antigen CD2 CD2 0.0132
4890 Hemagglutinin HA 0.0132
6566 Hemagglutinin Not Available 0.0132
4861 Interleukin-6 receptor alpha chain IL6R 0.0132
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0132
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0132
3837 Cytokine receptor common beta chain CSF2RB 0.0132
48 Pyridoxal kinase PDXK 0.0131
554 Low-density lipoprotein receptor LDLR 0.0123
3444 Cyanovirin-N Not Available 0.0122
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0122
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.0122
1859 Prostatic acid phosphatase ACPP 0.0122
3140 Hemagglutinin-neuraminidase HN 0.0122
3609 Hemagglutinin-neuraminidase HN 0.0122
2297 Genome polyprotein Not Available 0.0122
2322 Genome polyprotein Not Available 0.0122
2694 Genome polyprotein Not Available 0.0122
2719 Genome polyprotein Not Available 0.0122
2860 Genome polyprotein Not Available 0.0122
2928 Genome polyprotein Not Available 0.0122
3160 Genome polyprotein Not Available 0.0122
3260 Genome polyprotein Not Available 0.0122
4783 Genome polyprotein Not Available 0.0122
5726 Genome polyprotein Not Available 0.0122
5779 Genome polyprotein Not Available 0.0122
5867 Genome polyprotein Not Available 0.0122
6253 Genome polyprotein Not Available 0.0122
6301 Genome polyprotein Not Available 0.0122
6380 Genome polyprotein Not Available 0.0122
6381 Genome polyprotein Not Available 0.0122
6437 Genome polyprotein Not Available 0.0122
6520 Genome polyprotein Not Available 0.0122
6521 Genome polyprotein Not Available 0.0122
6652 Genome polyprotein Not Available 0.0122
6734 Genome polyprotein Not Available 0.0122
6735 Genome polyprotein Not Available 0.0122
6736 Genome polyprotein Not Available 0.0122
6737 Genome polyprotein Not Available 0.0122
6738 Genome polyprotein Not Available 0.0122
6739 Genome polyprotein Not Available 0.0122
6744 Genome polyprotein Not Available 0.0122
6748 Genome polyprotein Not Available 0.0122
6894 Genome polyprotein Not Available 0.0122
6898 Genome polyprotein Not Available 0.0122
852 Heparin cofactor 2 SERPIND1 0.0117
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.0116
4666 Fucose-binding lectin PA-IIL lecB 0.0115
2372 Bifunctional tail protein 9 0.0115
4787 Envelope glycoprotein gp160 env 0.0115
4820 Envelope glycoprotein gp160 env 0.0115
5727 Envelope glycoprotein gp160 env 0.0115
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.011
3480 Mannan endo-1,4-beta-mannosidase manA 0.0106
64 Neuraminidase NA 0.0106
641 Neuraminidase NA 0.0106
2676 Neuraminidase NA 0.0106
3026 Neuraminidase NA 0.0106
3519 Neuraminidase NA 0.0106
6007 Neuraminidase NA 0.0106
595 Fibrinogen alpha chain FGA 0.0104
1439 Lactotransferrin LTF 0.0103
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0101
2430 Chondroitinase B cslB 0.0098
6307 Ig gamma-2 chain C region IGHG2 0.0096
2581 Chondroitinase AC cslA 0.0096
6847 Lactase-phlorizin hydrolase LCT 0.0094
6500 Phospholipase A2 PLA2G1B 0.0092
309 Antithrombin-III SERPINC1 0.0091
2207 Rhodopsin RHO 0.0088
3814 Complement C1r subcomponent C1R 0.0084
4785 Ig gamma-1 chain C region IGHG1 0.0079
76 Nitric-oxide synthase, brain NOS1 0.0078
4604 Liver carboxylesterase 1 CES1 0.0075
952 Dipeptidyl peptidase 4 DPP4 0.0068
3794 Osmolarity sensor protein envZ envZ 0.0064
5644 Sensor protein phoQ phoQ 0.0064
5641 Rod shape-determining protein MreB TM_0588 0.0064
4178 DNA repair protein RAD51 homolog 1 RAD51 0.0064
5645 DNA topoisomerase 4 subunit B parE 0.0064
6227 DNA topoisomerase 4 subunit B parE 0.0064
5649 Potassium-transporting ATPase B chain kdpB 0.0064
5290 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0064
5638 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0064
5643 General secretion pathway protein E epsE 0.0064
5642 Chaperone clpB clpB 0.0064
3923 Cholinesterase BCHE 0.0059
2867 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase ispE 0.0056
3390 Aminoglycoside 3'-phosphotransferase aphA 0.0056
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.0056
6433 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 PFKFB4 0.0056
5302 TrwB trwB 0.0056
2282 Protein recA recA 0.0056
2315 Protein recA recA 0.0056
2332 Protein recA recA 0.0056
5263 Protein recA recA 0.0056
2397 Dihydroxyacetone kinase dhaK 0.0056
4751 Mitogen-activated protein kinase 12 MAPK12 0.0056
5646 Galactokinase GALK1 0.0056
2852 DNA mismatch repair protein mutL mutL 0.0056
740 Argininosuccinate synthase ASS1 0.0056
865 Argininosuccinate synthase ASS1 0.0056
2680 Argininosuccinate synthase argG 0.0056
3194 Argininosuccinate synthase argG 0.0056
5265 FtsH ftsH 0.0056
20 Prostaglandin G/H synthase 1 PTGS1 0.0054
4373 Medium-chain-fatty-acid--CoA ligase Not Available 0.0051
3231 Death-associated protein kinase 1 DAPK1 0.0051
887 DNA gyrase subunit B gyrB 0.0049
4150 DNA gyrase subunit B gyrB 0.0049
6225 DNA gyrase subunit B gyrB 0.0049
936 Ephrin type-A receptor 2 EPHA2 0.0049
2950 Inositol-trisphosphate 3-kinase A ITPKA 0.0048
2371 Pantothenate kinase coaA 0.0048
825 Arsenical pump-driving ATPase ASNA1 0.0048
3435 Arsenical pump-driving ATPase arsA 0.0048
2892 Acetylglutamate kinase argB 0.0048
3550 Acetylglutamate kinase argB 0.0048
1881 Hexokinase-1 HK1 0.0048
6832 Serine/threonine-protein kinase SRPK2 SRPK2 0.0047
2727 S-adenosylmethionine synthetase metK 0.0046
4192 DNA topoisomerase 2-beta TOP2B 0.0043
207 Glutathione synthetase GSS 0.0042
5269 Glutathione synthetase gshB 0.0042
2251 Thymidylate kinase tmk 0.0041
2254 Thymidylate kinase DTYMK 0.0041
3522 Thymidylate kinase tmk 0.0041
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.004
937 Proto-oncogene tyrosine-protein kinase LCK LCK 0.0038
3822 Actin, alpha skeletal muscle ACTA1 0.0038
1836 Mitogen-activated protein kinase 10 MAPK10 0.0036
1721 Glycogen synthase kinase-3 beta GSK3B 0.0035
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.0035
2236 Casein kinase II subunit alpha CSNK2A1 0.0034
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