Id: acc0417
Group: 1sens
Protein: IGF-IR
Gene Symbol: IGF1R
Protein Id: P08069
Protein Name: IGF1R_HUMAN
PTM: phosphorylation
Site: Tyr1131
Site Sequence: GMAYLNANKFVHRDLAARNCM
Disease Category: Cancer
Disease: Gastric Cancer
Disease Subtype:
Disease Cellline: SGC7901
Disease Info:
Drug: cetuximab
Drug Info: "Cetuximab is a recombinant human-mouse chimeric monoclonal antibody that specifically binds to the epidermal growth factor receptor (EGFR), competitively inhibiting ligand binding and blocking downstream signaling pathways, thereby inhibiting cancer cell proliferation, inducing apoptosis, and reducing the production of matrix metalloproteinases and vascular endothelial growth factor; it is used in combination with irinotecan for EGFR-positive, irinotecan-resistant metastatic colorectal cancer, as a monotherapy for patients intolerant to irinotecan, and in combination with radiotherapy for locally advanced head and neck squamous cell carcinoma. "
Effect: inhibit
Effect Info: "After treatment with the Src inhibitor PP2, the cetuximab-mediated phosphorylation of IGF-IR was significantly reduced, thereby restoring the sensitivity of gastric cancer cells to cetuximab."
Note:
Score: 5.0
Pubmed(PMID): 25625229
Sentence Index:
Sentence:

Sequence & Structure:

MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLHILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGDLCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCSAPDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHDGECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNLLINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSFYVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTRNNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDGQDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSEILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRHNYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRKVFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFESRVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTWEPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGNYTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHRKRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRHSGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target Drug name MOA Phase Status Disease Source
IGF1R TEPROTUMUMAB Insulin-like growth factor I receptor antagonist 4 - immune system disease ATC
IGF1R MASOPROCOL Insulin-like growth factor I receptor inhibitor 4 - neoplasm ATC
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 4 - hypothyroidism DailyMed
IGF1R TEPROTUMUMAB Insulin-like growth factor I receptor antagonist 4 - Graves ophthalmopathy DailyMed
FDA
IGF1R TEPROTUMUMAB Insulin-like growth factor I receptor antagonist 4 Completed Graves ophthalmopathy ClinicalTrials
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 4 - Growth delay DailyMed
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 4 - Laron syndrome EMA
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 3 Completed diabetes mellitus ClinicalTrials
IGF1R FIGITUMUMAB Insulin-like growth factor I receptor antagonist 3 Terminated squamous cell carcinoma ClinicalTrials
ClinicalTrials
IGF1R FIGITUMUMAB Insulin-like growth factor I receptor antagonist 3 Terminated non-small cell lung carcinoma ClinicalTrials
ClinicalTrials
IGF1R FIGITUMUMAB Insulin-like growth factor I receptor antagonist 3 Withdrawn non-small cell lung carcinoma ClinicalTrials
IGF1R FIGITUMUMAB Insulin-like growth factor I receptor antagonist 3 Terminated large cell lung carcinoma ClinicalTrials
ClinicalTrials
IGF1R TEPROTUMUMAB Insulin-like growth factor I receptor antagonist 3 Recruiting eye disease ClinicalTrials
IGF1R TEPROTUMUMAB Insulin-like growth factor I receptor antagonist 3 Completed eye disease ClinicalTrials
IGF1R LINSITINIB Insulin-like growth factor I receptor inhibitor 3 Completed adrenal cortex carcinoma ClinicalTrials
IGF1R TEPROTUMUMAB Insulin-like growth factor I receptor antagonist 3 Completed Graves ophthalmopathy ClinicalTrials
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 3 Completed Growth abnormality ClinicalTrials
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 3 Terminated Growth abnormality ClinicalTrials
IGF1R MECASERMIN Insulin-like growth factor I receptor agonist 3 Completed amyotrophic lateral sclerosis ClinicalTrials
IGF1R CIXUTUMUMAB Insulin-like growth factor I receptor antagonist 2 Completed hepatocellular carcinoma ClinicalTrials
IGF1R CIXUTUMUMAB Insulin-like growth factor I receptor antagonist 2 Completed head and neck squamous cell carcinoma ClinicalTrials
IGF1R LINSITINIB Insulin-like growth factor I receptor inhibitor 2 Completed Ewing sarcoma ClinicalTrials
IGF1R GANITUMAB Insulin-like growth factor I receptor antagonist 2 Completed Ewing sarcoma ClinicalTrials
IGF1R LINSITINIB Insulin-like growth factor I receptor inhibitor 2 Terminated hepatocellular carcinoma ClinicalTrials
IGF1R CIXUTUMUMAB Insulin-like growth factor I receptor antagonist 2 Completed alveolar rhabdomyosarcoma ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets
Small molecule
Antibody
PROTAC
Other modalities
Approved Drug
Advanced Clinical
Phase 1 Clinical
Structure with Ligand
High-Quality Ligand
High-Quality Pocket
Med-Quality Pocket
Druggable Family
Approved Drug
Advanced Clinical
Phase 1 Clinical
UniProt loc high conf
GO CC high conf
UniProt loc med conf
UniProt SigP or TMHMM
GO CC med conf
Human Protein Atlas loc
Approved Drug
Advanced Clinical
Phase 1 Clinical
Literature
UniProt Ubiquitination
Database Ubiquitination
Half-life Data
Small Molecule Binder
Approved Drug
Advanced Clinical
Phase 1 Clinical

PTM Intensity:

source: CPTAC
IGF1R-Ser1339
Cancer Intensity
BRCA 0.418
COAD
HGSC
ccRCC
GBM
HNSC 0.723
LUAD
LUSC -1.141
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
- - P Prostate cancer/carcinoma/adenocarcinoma Glycosylation 23724116
Y 1165 U Breast cancer/tumor/carcinoma Phosphorylation 23663564
Y 1166 U Breast cancer/tumor/carcinoma Phosphorylation 23663564
Y 980 U Ewing sarcoma Phosphorylation 36394520
Y 1135 U Ewing sarcoma Phosphorylation 36394520
Y 1136 U Ewing sarcoma Phosphorylation 36394520
Y 1161 U Neuroblastoma Phosphorylation 24349301
- - U Barrett's neoplasia Phosphorylation 14608530
K 1025 U Acute myelogenous leukemia SUMOylation 25448401
K 1100 U Acute myelogenous leukemia SUMOylation 25448401
- - U Non-small cell lung cancer Ubiquitination 33415003

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links: