Non-fucosylated Anti-Human EGFR (Necitumumab) Therapeutic Antibody (CAT#: BioBet-009ZP) Datasheet

EGFR

epidermal growth factor receptor

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer.

EGFR; epidermal growth factor receptor; ERBB; HER1; mENA; ERBB1; PIG61; NISBD2; proto-oncogene c-ErbB-1; cell growth inhibiting protein 40; erb-b2 receptor tyrosine kinase 1; cell proliferation-inducing protein 61; receptor tyrosine-protein kinase erbB-1; avian erythroblastic leukemia viral (v-erb-b) oncogene homolog

Plasma membrane, Extracellular region or secreted Cytosol, Endosome, Nucleus, Golgi apparatus, ER.

Diseases associated with EGFR include Inflammatory Skin And Bowel Disease, Neonatal, 2 and Lung Cancer.

Its related pathways are DAG and IP3 signaling and Association Between Physico-Chemical Features and Toxicity Associated Pathways.

1.Receptor tyrosine kinases bind to EGF family ligands and activate several signal cascades to transduce extracellular signals into appropriate cellular responses (PubMed: 2790960, PubMed: 10805725, PubMed: 27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG, and HBEGF/heparin binding EGF (PubMed: 2790960, PubMed: 7679104, PubMed: 8144591, PubMed: 9419975, PubMed :15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704). Ligand binding triggers homo- and/or heterodimerization of the receptor and autophosphorylation of key cytoplasmic residues. Phosphorylated receptors absorb adaptor proteins like GRB2, which in turn activate complex downstream signaling cascades. Activate at least 4 major downstream signal cascades, including RAS-RAF-MEK-ERK, PI3 kinase-akt, PLCgamma-PKC and STATs modules (PubMed: 27153536). It is also possible to activate the nf-kpa-b signal cascade (PubMed: 11116146). It can also directly phosphorylate other proteins such as RGS16 to activate its GTPase activity, and possibly couple EGF receptor signals with G protein-coupled receptor signals (PubMed: 11602604). It also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/ -catenin (PubMed: 11483589). Through the interaction with CCDC88A/GIV, it positively regulates cell migration, retains EGFR on the cell membrane after ligand stimulation, promotes EGFR signaling, and triggers cell migration (PubMed:20462955). Play a role in improving learning and memory performance (through similarity). 2. Isoform 2 can act as an antagonist of EGF. 3. (Microbial infection) It acts as a receptor for hepatitis C virus (HCV) in liver cells and promotes its entry into cells. HCV entry is mediated by promoting the formation of the CD81-CLDN1 receptor complex which is essential for HCV entry and enhancing the membrane fusion of cells expressing HCV envelope glycoprotein.

Cancer antibody; Signaling Transduction antibody

Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Dephosphorylated by PTPN1 and PTPN2. Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitination by OTUD7B prevents degradation. Ubiquitinated by RNF115 and RNF126 (By similarity). Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.

Protein Based Therapies
Monoclonal antibody (mAb)

IgG1

Necitumumab

Human

Human

Necitumumab (INN) is a recombinant human IgG1 monoclonal antibody used as an antitumor drug. It acts as an EGFR antagonist and binds to the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer (NSCLC).

Metastatic Non-Small Cell Lung Cancer

Not Available

Necitumumab is an EGFR antagonist that works by binding to the epidermal growth factor receptor (EGFR) and preventing its ligand from binding and is widely used to treat metastatic NSCLC. The binding of necitumumab to EGFR can induce receptor internalization and degradation. In vivo data in mouse model show that Necitumumab can target tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and increase antitumor activity.

Necitumumab is approved as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC) with cisplatin and gemcitabine.