Target Information
Target General Infomation | |||||
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Target ID |
T48069
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Former ID |
TTDS00269
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Target Name |
Insulin-like growth factor I receptor
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Gene Name |
IGF1R
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Synonyms |
CD221 antigen; IGF-1 receptor; IGF-1R; IGF-IR; Type 1 insulin-like growth factor receptor; IGF1R
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Target Type |
Successful
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Disease | Breast cancer [ICD9: 174, 175; ICD10: C50] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21] | |||||
Growth failure [ICD10: R62.8] | |||||
Graves' ophthalmopathy [ICD10: H06.2] | |||||
Hormone deficiency [ICD10: E00-E90] | |||||
Hepatocellular carcinoma; Non-small cell lung cancer [ICD9:155; ICD10: C22.0, C33-C34] | |||||
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.
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BioChemical Class |
Kinase
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Target Validation |
T48069
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UniProt ID | |||||
EC Number |
EC 2.7.10.1
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Sequence |
MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLH
ILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIF EMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGD LCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCS APDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHD GECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNL LINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSF YVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTR NNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDG QDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSE ILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRH NYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRK VFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFES RVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTW EPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGN YTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHR KRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKG VVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIME LMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARN CMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGV VLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFL EIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRH SGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC |
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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 521879 | ClinicalTrials.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 522702 | ClinicalTrials.gov (NCT00924989) A Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma. U.S. National Institutes of Health. | ||||
Ref 523234 | ClinicalTrials.gov (NCT01232452) A Study in Non-Small Cell Lung Cancer. U.S. National Institutes of Health. | ||||
Ref 523845 | ClinicalTrials.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 525130 | ClinicalTrials.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 525958 | A 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 536361 | Natural 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 544191 | Potent inhibitory effect of the cyclolignan picropodophyllin (PPP) on human adrenocortical carcinoma cells proliferation. Am J Cancer Res. 2011; 1(3): 356-361. | ||||
Ref 547388 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015801) | ||||
Ref 547863 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019974) | ||||
Ref 547948 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020634) | ||||
Ref 548064 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021633) | ||||
Ref 548102 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021953) | ||||
Ref 548135 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022289) | ||||
Ref 548302 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024318) | ||||
Ref 548559 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026610) | ||||
Ref 548652 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027382) | ||||
Ref 548938 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030562) | ||||
Ref 525958 | A 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 527486 | 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. | ||||
Ref 528746 | Eur 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 528935 | The 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 529668 | J 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 530338 | Insulin-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 530722 | Bioorg 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 530811 | Bioorg 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 531096 | Clinical 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 532567 | MM-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 532644 | A 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 533208 | Doxorubicin 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 535735 | One 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 535760 | IGF-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 535800 | Insulin-like growth factor I receptor gene structure. J Biol Chem. 1992 May 25;267(15):10759-63. | ||||
Ref 536311 | Analysis of the human type I insulin-like growth factor receptor promoter region. Biochem Biophys Res Commun. 1991 Jun 28;177(3):1113-20. | ||||
Ref 536474 | A 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 536624 | FAK 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 536900 | Co-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 537226 | AMG 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 548988 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031207) | ||||
Ref 549834 | BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009. |
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