Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.

Binding multiple sites within proteins with bivalent compounds is a strategy for developing uniquely active agents. A new class of dual-site inhibitors has emerged targeting the epidermal growth factor receptor (EGFR) anchored to both the orthosteric (ATP) and allosteric sites. Despite proof-of-concept successes, enabling selectivity against oncogenic activating mutations has not been achieved and classifying these inhibitors among kinase inhibitors remains underexplored.

Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.

Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual motif architecture of these molecules and the variability that can be introduced through differing linker structures and geometries. We report a set of alternatively linked bivalent EGFR inhibitors that simultaneously occupy the ATP substrate and allosteric pockets.

Magnetic Properties of CoFeO Thin Films Synthesized by Radical-Enhanced Atomic Layer Deposition.

A radical-enhanced atomic layer deposition (RE-ALD) process was developed for growing ferrimagnetic CoFeO thin films. By utilizing bis(2,2,6,6-tetramethyl-3,5-heptanedionato) cobalt(II), tris(2,2,6,6-tetramethyl-3,5-heptanedionato) iron(III), and atomic oxygen as the metal and oxidation sources, respectively, amorphous and stoichiometric CoFeO films were deposited onto SrTiO (001) substrates at 200 °C. The RE-ALD growth rate obtained for CoFeO is ∼2.