Mechanistic Study of Potent Fluorinated EGFR Kinase Inhibitors with a Quinazoline Scaffold against L858R/T790M/C797S Resistance Mutation: Unveiling the Fluorine Substituent Cooperativity Effect on the Inhibitory Activity

2020 ◽  
Vol 124 (28) ◽  
pp. 5813-5824
Author(s):  
Farideh Badichi Akher ◽  
Abdolkarim Farrokhzadeh ◽  
Neil Ravenscroft ◽  
Michelle M. Kuttel
Keyword(s):  
Inhibitory Activity ◽  
Kinase Inhibitors ◽  
Resistance Mutation ◽  
Mechanistic Study ◽  
Cooperativity Effect ◽  
Egfr Kinase

Syntheses and EGFR Kinase Inhibitory Activity of 6-Substituted-4-anilino [1,7] and [1,8] Naphthyridine-3-carbonitriles.

ChemInform ◽  
2004 ◽  
Vol 35 (30) ◽  
Author(s):  
Allan Wissner ◽  
Philip R. Hamann ◽  
Ramaswamy Nilakantan ◽  
Lee M. Greenberger ◽  
Fei Ye ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Kinase Inhibitory Activity ◽  
Egfr Kinase

scholarly journals Descriptor-Based Profile Analysis of Kinase Inhibitors to Predict Inhibitory Activity and to Grasp Kinase Selectivity

2013 ◽  
Vol 34 (9) ◽  
pp. 2680-2684
Author(s):  
Hyejin Park ◽  
Kyeung Kyu Kim ◽  
ChangHoon Kim ◽  
Jae-Min Shin ◽  
Kyoung Tai No
Keyword(s):  
Inhibitory Activity ◽  
Kinase Inhibitors ◽  
Profile Analysis

scholarly journals Platination of cysteine by an epidermal growth factor receptor kinase-targeted hybrid agent

2018 ◽  
Vol 54 (54) ◽  
pp. 7479-7482 ◽  
Author(s):  
Mu Yang ◽  
Hanzhi Wu ◽  
Julie Chu ◽  
Lucas A. Gabriel ◽  
Y. Kim ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Cysteine Residue ◽  
Receptor Kinase ◽  
Epidermal Growth ◽  
Hybrid Agent ◽  
Egfr Kinase

Platinum-modified tyrosine kinase inhibitors show strong and selective EGFR kinase binding and form adducts with a pharmacologically relevant cysteine residue.

scholarly journals Discovery of Potent and Noncovalent Reversible EGFR Kinase Inhibitors of EGFRL858R/T790M/C797S

2019 ◽  
Vol 10 (6) ◽  
pp. 869-873 ◽  
Author(s):  
Qiannan Li ◽  
Tao Zhang ◽  
Shiliang Li ◽  
Linjiang Tong ◽  
Junyu Li ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Kinase

scholarly journals Non-Small-Cell Lung Cancer-Sensitive Detection of the p.Thr790Met EGFR Alteration by Preamplification before PNA-Mediated PCR Clamping and Pyrosequencing

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 527
Author(s):  
Amandine Billaud ◽  
Veronique Verriele ◽  
Jonathan Dauvé ◽  
Louise-Marie Chevalier ◽  
Alain Morel
Keyword(s):  
First Generation ◽  
Kinase Inhibitors ◽  
Resistance Mutation ◽  
Small Cell ◽  
Therapeutic Management ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Ffpe Samples ◽  
Egfr Tyrosine Kinase Inhibitors

Targeted therapies and, more precisely, EGFR tyrosine kinase inhibitors (TKIs) have been a major improvement in the therapeutic management of EGFR-mutated non-small-cell lung cancers (NSCLCs). Earlier administration of these TKIs throughout tumor progression is imperative to improve patient outcomes. Consequently, studies have focused on refining the characterization of biomarkers, especially concerning the resistance mutation p.Thr790Met of EGFR. Herein, we developed peptide nucleic acid (PNA)-mediated PCR clamping followed by pyrosequencing, favoring enrichment of the mutated fraction. A preamplification step was first added to increase the amplifiable DNA fraction. Throughout the application of our method on DNA extracted from FFPE samples of 46 patients with NSCLC who had relapsed under first-generation EGFR TKI, we evaluated a sensitivity of 93.3% and a specificity of 100%. All 19 patients who were positive for the p.Thr790Met mutation with NGS were also found to be positive with our protocol. The only discordant case was a sample with no mutation detected with NGS, but which was positive with PNA. This protocol allows for the detection of the p.Thr790Met mutation with a sensitivity of 0.5% which will permit earlier detection and an improvement of therapeutic management.

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