Therapeutic Targets Database
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TTD Target ID: TTDS00269

Target Information
NameInsulin-like growth factor I receptor    
Type of targetSuccessful target    
SynonymsCD221 antigen    
IGF-1 receptor    
IGF-1R    
IGF-IR    
Type 1 insulin-like growth factor receptor    
DiseaseCancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[1]
Colorectal cancer
[ICD9: 153, 154   ICD10: C18-C21]
[2]
Ewing's sarcoma
[ICD9: 170   ICD10: C41]
[3]
Medulloblastoma
[ICD9: 191   ICD10: C71]
[4]
Peripheral neuroectodermal tumor
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[3]
Tumors
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[5][6]
Drug(s)MecaserminApprovedIGF-1 deficiency[7][8][9][10]
FigitumumabPhase IIINon-Small Cell Lung Cancer (Biologic)[11][12]
AMG 479Phase IICancers[13][14]
CixutumumabPhase IIOn-small cell lung cancer
FigitumumabPhase IIGastrointestinal Cancers; Genitourinary; Ewing's Sarcoma; Small Cell Lung Cancer; Breast Cancer (Biologic)[11][12]
MK-0646Phase IICancer[15][16]
AEW-541Phase IVarious cancers, multiple myeloma[17][18][19]
R1507Suspended in Phase IINSCLC, Ewing's sarcoma and metastatic breast cancer[20][21]
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.112
PathwayAdherens junction
Colorectal cancer
Focal adhesion
Glioma
Long-term depression
Melanoma
Pathways in cancer
Prostate cancer
UniProt IDP08069
PDB Structure1IGR; 1JQH; 1K3A; 1M7N; 1P4O; 2OJ9; 2ZM3; 3D94; 3F5P; 3I81; 3LVP; 3LW0; 3NW5; 3NW6; 3NW7; 3O23; 3QQU.    
FunctionThis receptor binds insulin-like growth factor I (IGF I) with a high affinity and igf ii with a lower affinity. It has a tyrosine-protein kinase activity.    
SequenceMKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLH ILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIF EMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGD LCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCS APDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHD GECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNL LINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSF YVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTR NNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDG QDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSE ILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRH NYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRK VFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFES RVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTW EPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGN YTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHR KRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKG VVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIME LMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARN CMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGV VLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFL EIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRH SGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC
Related US Patent6,645,775
6,677,305
Target ValidationClick to Find Target Validation Information.    
Inhibitor4- ([22]
4- ([22]
AEW-541[17][18][19]
AMG 479[13][14]
Alpha-D-Mannose[23]
BMS-536924[24]
BMS-695735[25]
Figitumumab[11][12]
Fucose[23]
JB-1[26]
MK-0646[15][16]
Mecasermin[7][8][9][10]
NVP-ADW742[26]
OSI-906[27]
Phosphoaminophosphonic Acid-Adenylate Ester[28]
R1507[20][21]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1The IGF-1 receptor in cancer biology. Int J Cancer. 2003 Dec 20;107(6):873-7. To Reference
Ref 2Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. Br J Cancer. 2000 May;82(10):1724-31. To Reference
Ref 3Insulin-like growth factor I receptor-mediated circuit in Ewing's sarcoma/peripheral neuroectodermal tumor: a possible therapeutic target. Cancer Res. 1996 Oct 15;56(20):4570-4. To Reference
Ref 4Insulin-like growth factor-I receptor - a potential therapeutic target in medulloblastomas. Expert Opin Ther Targets. 2002 Oct;6(5):539-44. To Reference
Ref 5The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. Crit Rev Oncog. 1997;8(1):71-92. To Reference
Ref 6Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor. Oncogene. 2003 Sep 29;22(42):6589-97. To Reference
Ref 7IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Virchows Arch. 2003 Aug;443(2):139-45. Epub 2003 Jul 5. To Reference
Ref 8One of two chondrocyte-expressed isoforms of cartilage intermediate-layer protein functions as an insulin-like growth factor 1 antagonist. Arthritis Rheum. 2003 May;48(5):1302-14. To Reference
Ref 9Analysis of the human type I insulin-like growth factor receptor promoter region. Biochem Biophys Res Commun. 1991 Jun 28;177(3):1113-20. To Reference
Ref 10Insulin-like growth factor I receptor gene structure. J Biol Chem. 1992 May 25;267(15):10759-63. To Reference
Ref 11Pfizer. Product Development Pipeline. March 31 2009. To Reference
Ref 12National Cancer Institute. NCI Drug Dictionary. 2009 To Reference
Ref 13Amgen. Product Development Pipeline. February 6 2009. To Reference
Ref 14AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells. Mol Cancer Ther. 2009 Apr 14. [Epub ahead of print] To Reference
Ref 15Merck. Product Development Pipeline. July 15 2009. To Reference
Ref 16Merck. Report of Merck. March 2009. To Reference
Ref 17A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. To Reference
Ref 18Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. Int J Oncol. 2008 Nov;33(5):1107-13. To Reference
Ref 19FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells. Carcinogenesis. 2008 Jun;29(6):1096-107. Epub 2008 Feb 7. To Reference
Ref 20Roche. Product Development Pipeline. July 29 2009. To Reference
Ref 21National Cancer Institute. Dictionary of Cancer Terms. 2009 To Reference
Ref 22Eur J Pharmacol. 2007 May 7;562(1-2):1-11. Epub 2007 Feb 3.ATP non-competitive IGF-1 receptor kinase inhibitors as lead anti-neoplastic and anti-papilloma agents. To Reference
Ref 23Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 24Bioorg Med Chem Lett. 2010 Mar 1;20(5):1744-8. Epub 2010 Jan 21.SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors. To Reference
Ref 25J Med Chem. 2008 Oct 9;51(19):5897-900. Epub 2008 Sep 3.Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (BMS-695735), an orally efficacious inhibitor of insulin-like growth factor-1 receptor kinase with broad spectrum in vivo antitumor activity. To Reference
Ref 26Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. To Reference
Ref 27Bioorg Med Chem Lett. 2010 Apr 15;20(8):2452-5. Epub 2010 Mar 7.Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family of receptor tyrosine kinases. To Reference
Ref 28Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference



 

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