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Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors. | LitMetric

Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors.

Cell Chem Biol

Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; Department of Oncology, McGill University, Montreal, Canada; Rosalind & Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada. Electronic address:

Published: November 2019

AI Article Synopsis

Article Abstract

Rocaglates share a common cyclopenta[b]benzofuran core that inhibits eukaryotic translation initiation by modifying the behavior of the RNA helicase, eIF4A. Working as interfacial inhibitors, rocaglates stabilize the association between eIF4A and RNA, which can lead to the formation of steric barriers that block initiating ribosomes. There is significant interest in the development and expansion of rocaglate derivatives, as several members of this family have been shown to possess potent anti-neoplastic activity in vitro and in vivo. To further our understanding of rocaglate diversity and drug design, herein we explore the RNA clamping activity of >200 unique rocaglate derivatives. Through this, we report on the identification and characterization of a potent class of synthetic rocaglates called amidino-rocaglates. These compounds are among the most potent rocaglates documented to date and, taken together, this work offers important information that will guide the future design of rocaglates with improved biological properties.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874763PMC
http://dx.doi.org/10.1016/j.chembiol.2019.08.008DOI Listing

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