174709-17-2Relevant articles and documents
Studying the Conformation of a Receptor Tyrosine Kinase in Solution by Inhibitor-Based Spin Labeling
Yin, Dongsheng M.,Hannam, Jeffrey S.,Schmitz, Anton,Schiemann, Olav,Hagelueken, Gregor,Famulok, Michael
, p. 8417 - 8421 (2017/07/11)
The synthesis of a spin label based on PD168393, a covalent inhibitor of a major anticancer drug target, the epidermal growth factor receptor (EGFR), is reported. The label facilitates the analysis of the EGFR structure in solution by pulsed electron paramagnetic resonance (EPR) spectroscopy. For various EGFR constructs, including near-full-length EGFR, we determined defined distance distributions between the two spin labels bound to the ATP binding sites of the EGFR dimer. The distances are in excellent agreement with an asymmetric dimer of the EGFR. Based on crystal structures, this dimer had previously been proposed to reflect the active conformation of the receptor but structural data demonstrating its existence in solution have been lacking. More generally, our study provides proof-of-concept that inhibitor-based spin labeling enables the convenient introduction of site-specific spin labels into kinases for which covalent or tight-binding small-molecule modulators are available.
Modified PEG-anilinoquinazoline derivatives as potential EGFR PET agents
Dissoki, Samar,Eshet, Renana,Billauer, Hana,Mishani, Eyal
body text, p. 41 - 52 (2009/12/01)
Inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) has emerged as a major approach for cancer-targeted therapy. Consequently, there has been a great interest in the use of labeled EGFR-TK inhibitors as positron emission tomography (P
