Target General Infomation
Target ID
T48069
Former ID
TTDS00269
Target Name
Insulin-like growth factor I receptor
Gene Name
IGF1R
Synonyms
CD221 antigen; IGF-1 receptor; IGF-1R; IGF-IR; Type 1 insulin-like growth factor receptor; IGF1R
Target Type
Successful
Disease Breast cancer [ICD9: 174, 175; ICD10: C50]
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Growth failure [ICD10: R62.8]
Graves' ophthalmopathy [ICD10: H06.2]
Hepatocellular carcinoma; Non-small cell lung cancer [ICD9:155; ICD10: C22.0, C33-C34]
Hormone deficiency [ICD10: E00-E90]
Liver cancer; Non-small cell lung cancer [ICD9:140-229, 155, 203.0; ICD10: C22, C33-C34]
Motor neurone disease [ICD9: 335.2; ICD10: G12.2]
Malignant adrenal gland cancer [ICD10: C74.0]
Multiple myeloma [ICD9: 203; ICD10: C90]
Non-small cell lung cancer [ICD10: C33-C34]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
BioChemical Class
Kinase
Target Validation
T48069
UniProt ID
EC Number
EC 2.7.10.1
Sequence
MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLH
ILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIF
EMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGD
LCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCS
APDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHD
GECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNL
LINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSF
YVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTR
NNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDG
QDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSE
ILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRH
NYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRK
VFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFES
RVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTW
EPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGN
YTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHR
KRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKG
VVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIME
LMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARN
CMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGV
VLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFL
EIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRH
SGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC
Drugs and Mode of Action
Drug(s) Mecasermin Drug Info Approved Growth failure [536361], [551186]
Somatomedin-1 Drug Info Approved Hormone deficiency [551871]
OSI-906 Drug Info Phase 3 Solid tumours [522702], [542447]
Rinfabate Drug Info Phase 2/3 Cancer [521879]
AMG 479 Drug Info Phase 2 Breast cancer [548302]
AXL-1717 Drug Info Phase 2 Cancer [523845], [542799]
Cixutumumab Drug Info Phase 2 Liver cancer; Non-small cell lung cancer [523234]
MM-141 Drug Info Phase 2 Cancer [525130]
R1507 Drug Info Phase 2 Graves' ophthalmopathy [547388]
TT-100 Drug Info Phase 2 Non-small cell lung cancer [548064]
AEW-541 Drug Info Phase 1 Multiple myeloma [547863]
BIIB 022 Drug Info Phase 1 Hepatocellular carcinoma; Non-small cell lung cancer [548652]
Cyclolignan picropodophyllin Drug Info Phase 1 Colorectal cancer [544191]
HF-0299 Drug Info Phase 1 Pain [525958]
RG-7010 Drug Info Phase 1 Motor neurone disease [548987]
BMS-695735 Drug Info Preclinical Solid tumours [548135]
EGFR/IGFR tandem adnectin Drug Info Preclinical Cancer [548559]
AVE-1642 Drug Info Discontinued in Phase 2 Breast cancer [548102]
KW-2450 Drug Info Discontinued in Phase 1/2 Breast cancer [548938]
Figitumumab Drug Info Discontinued in Phase 1 Malignant adrenal gland cancer [547948]
Inhibitor 4-((1H-indazol-6-ylamino)methyl)benzene-1,2-diol Drug Info [528746]
4-((naphthalen-2-ylamino)methyl)benzene-1,2-diol Drug Info [528746]
AEW-541 Drug Info [536474], [536624], [536900]
Alpha-D-Mannose Drug Info [551393]
AMG 479 Drug Info [537226], [550250]
AXL-1717 Drug Info [531096]
BMS-536924 Drug Info [530722]
BMS-695735 Drug Info [529668]
Cyclolignan picropodophyllin Drug Info [528935]
EGFR/IGFR tandem adnectin Drug Info [550011]
Figitumumab Drug Info [549974], [550522]
Fucose Drug Info [551393]
JB-1 Drug Info [537114]
Mecasermin Drug Info [535735], [535760], [535800], [536311]
NVP-ADW742 Drug Info [537114]
OSI-906 Drug Info [530811]
Phosphoaminophosphonic Acid-Adenylate Ester Drug Info [551374]
R1507 Drug Info [550521], [551607]
TT-100 Drug Info [549834]
Antagonist BIIB 022 Drug Info [532644]
Modulator Cixutumumab Drug Info [533208]
HF-0299 Drug Info [525958]
KW-2450 Drug Info [1572591]
MM-141 Drug Info [532567]
RG-7010 Drug Info [548988]
Rinfabate Drug Info [527486]
Somatomedin-1 Drug Info [551186]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Ras signaling pathway
Rap1 signaling pathway
HIF-1 signaling pathway
FoxO signaling pathway
Oocyte meiosis
Endocytosis
PI3K-Akt signaling pathway
AMPK signaling pathway
Focal adhesion
Adherens junction
Signaling pathways regulating pluripotency of stem cells
Long-term depression
Ovarian steroidogenesis
Progesterone-mediated oocyte maturation
Pathways in cancer
Transcriptional misregulation in cancer
Proteoglycans in cancer
Glioma
Prostate cancer
Melanoma
PANTHER Pathway Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade
Insulin/IGF pathway-protein kinase B signaling cascade
Pathway Interaction Database Plasma membrane estrogen receptor signaling
SHP2 signaling
IGF1 pathway
Posttranslational regulation of adherens junction stability and dissassembly
Integrins in angiogenesis
Stabilization and expansion of the E-cadherin adherens junction
Reactome IRS-related events triggered by IGF1R
SHC-related events triggered by IGF1R
WikiPathways Senescence and Autophagy in Cancer
Insulin Signaling
Endochondral Ossification
Focal Adhesion
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
Apoptosis
Signaling Pathways in Glioblastoma
TSH signaling pathway
MicroRNAs in cardiomyocyte hypertrophy
References
Ref 521879ClinicalTrials.gov (NCT00368173) IGF-I/IGFBP-3 Therapy in Children and Adolescents With Growth Hormone Insenitivity Syndrome (GHIS) Such as Laron Syndrome. U.S. National Institutes of Health.
Ref 522702ClinicalTrials.gov (NCT00924989) A Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma. U.S. National Institutes of Health.
Ref 523234ClinicalTrials.gov (NCT01232452) A Study in Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 523845ClinicalTrials.gov (NCT01561456) Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung. U.S. National Institutes of Health.
Ref 525130ClinicalTrials.gov (NCT02399137) A Phase 2 Study of MM-141 Plus Nab-paclitaxel and Gemcitabine in Front-line Metastatic Pancreatic Cancer. U.S. National Institutes of Health.
Ref 525958A primary adrenal steroid, 11beta-hydroxyandrostenedione, has an osteotropic effect and little androgenic activity. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):203-11.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 542447(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7423).
Ref 542799(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7873).
Ref 544191Potent inhibitory effect of the cyclolignan picropodophyllin (PPP) on human adrenocortical carcinoma cells proliferation. Am J Cancer Res. 2011; 1(3): 356-361.
Ref 547388Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015801)
Ref 547863Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019974)
Ref 547948Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020634)
Ref 548064Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021633)
Ref 548102Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021953)
Ref 548135Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022289)
Ref 548302Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024318)
Ref 548559Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026610)
Ref 548652Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027382)
Ref 548938Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030562)
Ref 548987Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031207)
Ref 5511862005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref
Ref 525958A primary adrenal steroid, 11beta-hydroxyandrostenedione, has an osteotropic effect and little androgenic activity. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):203-11.
Ref 527486Mecasermin 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.
Ref 528746Eur 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.
Ref 528935The cyclolignan picropodophyllin attenuates intimal hyperplasia after rat carotid balloon injury by blocking insulin-like growth factor-1 receptor signaling. J Vasc Surg. 2007 Jul;46(1):108-15.
Ref 529668J 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.
Ref 530338Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growthfactor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin Cancer Res. 2009 Sep 1;15(17):5445-56.
Ref 530722Bioorg 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.
Ref 530811Bioorg 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.
Ref 531096Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7.
Ref 532567MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014 Feb;13(2):410-25.
Ref 532644A phase 1, open-label, dose-escalation study of BIIB022 (anti-IGF-1R monoclonal antibody) in subjects with relapsed or refractory solid tumors. Invest New Drugs. 2014 Jun;32(3):518-25.
Ref 533208Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model. Ann Oncol. 2015 Jul;26(7):1459-64.
Ref 535735One 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.
Ref 535760IGF-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.
Ref 535800Insulin-like growth factor I receptor gene structure. J Biol Chem. 1992 May 25;267(15):10759-63.
Ref 536311Analysis of the human type I insulin-like growth factor receptor promoter region. Biochem Biophys Res Commun. 1991 Jun 28;177(3):1113-20.
Ref 536474A 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.
Ref 536624FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells. Carcinogenesis. 2008 Jun;29(6):1096-107. Epub 2008 Feb 7.
Ref 536900Co-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.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 537226AMG 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.
Ref 548988Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031207)
Ref 549834BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
Ref 549974Pfizer. Product Development Pipeline. March 31 2009.
Ref 550011Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
Ref 550250Clinical pipeline report, company report or official report of Amgen (2009).
Ref 550521National Cancer Institute. Dictionary of Cancer Terms. 2009.
Ref 550522National Cancer Institute. NCI Drug Dictionary. 2009 (CdrID=456793)
Ref 5511862005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551607Clinical pipeline report, company report or official report of Roche (2009).
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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