Datasheet

生物学的記述

Specificity	EGF Receptor (E746-A750del Specific) Antibody [L24P14] detects endogenous levels of total EGF E746-A750del mutant Receptor protein.
Background	EGF Receptor (E746-A750del Specific) is a common exon 19 in-frame deletion mutation in the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase of the ErbB/HER family, resulting in the loss of five amino acids (Glu746-Ala750) from the kinase domain’s C-helix proximal region and accounting for about 90% of exon 19 deletions in non-small cell lung cancer (NSCLC). This deletion (c.2236_2250del15) repositions the C-helix N-terminally toward the N-lobe, stabilizing an active αC-β4 kinase conformation, which increases ATP-site accessibility and promotes allosteric asymmetric dimerization for trans-autophosphorylation. As a result, E746-A750del leads to ligand-independent constitutive kinase activation, hyperstimulating oncogenic signaling cascades such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, and PLCγ to drive tumor growth, invasion, and metastasis, especially in EGFR-mutant NSCLC among non-smokers. Clinically, this mutation predicts high sensitivity to first- and third-generation tyrosine kinase inhibitors (TKIs) like osimertinib, although secondary T790M mutation can confer drug resistance.

Specificity

EGF Receptor (E746-A750del Specific) Antibody [L24P14] detects endogenous levels of total EGF E746-A750del mutant Receptor protein.

Background

EGF Receptor (E746-A750del Specific) is a common exon 19 in-frame deletion mutation in the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase of the ErbB/HER family, resulting in the loss of five amino acids (Glu746-Ala750) from the kinase domain’s C-helix proximal region and accounting for about 90% of exon 19 deletions in non-small cell lung cancer (NSCLC). This deletion (c.2236_2250del15) repositions the C-helix N-terminally toward the N-lobe, stabilizing an active αC-β4 kinase conformation, which increases ATP-site accessibility and promotes allosteric asymmetric dimerization for trans-autophosphorylation. As a result, E746-A750del leads to ligand-independent constitutive kinase activation, hyperstimulating oncogenic signaling cascades such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, and PLCγ to drive tumor growth, invasion, and metastasis, especially in EGFR-mutant NSCLC among non-smokers. Clinically, this mutation predicts high sensitivity to first- and third-generation tyrosine kinase inhibitors (TKIs) like osimertinib, although secondary T790M mutation can confer drug resistance.

使用情報

Application

WB, IP, IHC, IF, FCM

Dilution

WB	IP	IHC	IF	FCM
1:1000	1:100	1:100 - 1:400	1:100 - 1:200	1:250 - 1:1000

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

175 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/34319231/
https://pubmed.ncbi.nlm.nih.gov/24019492/

Application Data

WB

Validated by Selleck

Lane 1: H3255, Lane 2: H1975, Lane 3: NCI-H1650