We present aryl pyrimidones and styryl quinazolines as self-reporting fluorescent ligands targeting the EGFR/ERBB family of receptor tyrosine kinases. Receptor tyrosine kinases (RTKs) are transmembrane proteins that play a key role in signaling pathways that are essential for cellular development and metabolism. Their dysregulation (overexpression, mutations, hyperactivity) has been implicated in several cancers. As part of our ongoing effort to generate new molecular tools to study RTK activation and signaling pathways, we have synthesized novel fluorescent ligands targeting these kinases. Two classes of probes will be described: the first is based on a pyrimidine core, as it represents one of the most prevalent, biologically relevant and pharmacologically active compounds. The second is based on a quinazoline core which is a well demonstrated pharmacophore in many RTK inhibitors such as lapatinib, erlotinib, gefitinib, etc. The optical properties, switching behavior and biophysical profiles of the probes will also be presented.

Development of �turn-on� fluorescent nucleobase mimics as kinase inhibitors

246th National Meeting (2013)

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