Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ6B2I)

DTT Name Epidermal growth factor receptor variant III (EGFR vIII)
Synonyms ERBB1 variant III; ERBB variant III
Gene Name EGFR
DTT Type
Clinical trial target
 [1]
BioChemical Class
Kinase
UniProt ID
EGFR_HUMAN
TTD ID
T64969
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.10.1
Sequence
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV
VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA
VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF
QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC
TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV
VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK
NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF
ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL
FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN
LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM
GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV
ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS
GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI
CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA
RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY
GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK
FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ
QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED
SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN
TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV
APQSSEFIGA
Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance (By similarity).
KEGG Pathway
EGFR tyrosine kinase inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
Calcium signaling pathway (hsa04020 )
HIF-1 signaling pathway (hsa04066 )
FoxO signaling pathway (hsa04068 )
Phospholipase D signaling pathway (hsa04072 )
Endocytosis (hsa04144 )
PI3K-Akt signaling pathway (hsa04151 )
Focal adhesion (hsa04510 )
Adherens junction (hsa04520 )
Gap junction (hsa04540 )
JAK-STAT signaling pathway (hsa04630 )
Regulation of actin cytoskeleton (hsa04810 )
GnRH signaling pathway (hsa04912 )
Estrogen signaling pathway (hsa04915 )
Oxytocin signaling pathway (hsa04921 )
Relaxin signaling pathway (hsa04926 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Cushing syndrome (hsa04934 )
Epithelial cell signaling in Helicobacter pylori infection (hsa05120 )
Shigellosis (hsa05131 )
Hepatitis C (hsa05160 )
Human cytomegalovirus infection (hsa05163 )
Human papillomavirus infection (hsa05165 )
Coronavirus disease - COVID-19 (hsa05171 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Melanoma (hsa05218 )
Bladder cancer (hsa05219 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Reactome Pathway
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382 )
Signaling by ERBB4 (R-HSA-1236394 )
SHC1 events in ERBB2 signaling (R-HSA-1250196 )
PLCG1 events in ERBB2 signaling (R-HSA-1251932 )
PIP3 activates AKT signaling (R-HSA-1257604 )
Signaling by EGFR (R-HSA-177929 )
GRB2 events in EGFR signaling (R-HSA-179812 )
GAB1 signalosome (R-HSA-180292 )
SHC1 events in EGFR signaling (R-HSA-180336 )
EGFR downregulation (R-HSA-182971 )
GRB2 events in ERBB2 signaling (R-HSA-1963640 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
EGFR interacts with phospholipase C-gamma (R-HSA-212718 )
EGFR Transactivation by Gastrin (R-HSA-2179392 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
Signal transduction by L1 (R-HSA-445144 )
Constitutive Signaling by EGFRvIII (R-HSA-5637810 )
Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303 )
RAF/MAP kinase cascade (R-HSA-5673001 )
ERBB2 Regulates Cell Motility (R-HSA-6785631 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
ERBB2 Activates PTK6 Signaling (R-HSA-8847993 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )
Clathrin-mediated endocytosis (R-HSA-8856828 )
PTK6 promotes HIF1A stabilization (R-HSA-8857538 )
Downregulation of ERBB2 signaling (R-HSA-8863795 )
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910 )
Extra-nuclear estrogen signaling (R-HSA-9009391 )
NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507 )
HCMV Early Events (R-HSA-9609690 )
Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Signaling by ERBB2 ECD mutants (R-HSA-9665348 )
Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686 )
Signaling by ERBB2 (R-HSA-1227986 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
11 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Anti-EGFR V III CAR-T cells DM8EAGV Glioma 2A00.0 Phase 1/2 [2]
Anti-EGFRvIII CAR transduced PBL DMDKTYU Brain cancer 2A00 Phase 1/2 [1]
EGFRvIII CAR DMC284G Glioblastoma multiforme 2A00.0 Phase 1/2 [3]
AMG 596 DM4G1SP Glioblastoma multiforme 2A00.0 Phase 1 [4]
Anti-EGFRvIII CAR T cells DM73920 Glioblastoma multiforme 2A00.0 Phase 1 [5]
CAR-T cells targeting EGFRviii DMRSG04 Glioblastoma multiforme 2A00.0 Phase 1 [6]
CART-EGFRvIII T cells DMGPR1C Recurrent glioblastoma 2A00.00 Phase 1 [7]
D2C7 DMIMK84 Glioblastoma of brain 2A00.00 Phase 1 [8]
EGFRvIII CAR T cells DM6XWV4 Glioblastoma multiforme 2A00.0 Phase 1 [9]
EGFRvIII-CARs DMA46RN Recurrent glioblastoma 2A00.00 Phase 1 [10]
RG6156 DMPKZX7 Glioblastoma 2A00 Phase 1 [11]
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⏷ Show the Full List of 11 Clinical Trial Drug(s)

References

1 ClinicalTrials.gov (NCT01454596) CAR T Cell Receptor Immunotherapy Targeting EGFRvIII for Patients With Malignant Gliomas Expressing EGFRvIII. U.S. National Institutes of Health.
2 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
3 EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Cancer Res. 2014 Feb 15;20(4):972-84.
4 Clinical pipeline report, company report or official report of Amgen.
5 ClinicalTrials.gov (NCT02844062) Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme
6 ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.
7 ClinicalTrials.gov (NCT02209376) Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
8 Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. J Immunother Cancer. 2019 May 29;7(1):142.
9 ClinicalTrials.gov (NCT02664363) EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma
10 ClinicalTrials.gov (NCT03283631) Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM
11 Clinical pipeline report, company report or official report of Roche