1. A comparative study of small molecules targeting eIF4A.
- Author
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Naineni SK, Itoua Maïga R, Cencic R, Putnam AA, Amador LA, Rodriguez AD, Jankowsky E, and Pelletier J
- Subjects
- Antineoplastic Agents pharmacology, Benzofurans chemistry, Cell Proliferation drug effects, Cell Survival drug effects, Epoxy Compounds chemistry, Eukaryotic Initiation Factor-4A antagonists & inhibitors, Eukaryotic Initiation Factor-4F antagonists & inhibitors, Eukaryotic Initiation Factor-4F chemistry, Humans, Macrolides chemistry, Neoplasms genetics, Phosphatidylinositol 3-Kinases genetics, Protein Biosynthesis drug effects, Proto-Oncogene Proteins c-akt genetics, Small Molecule Libraries pharmacology, Sterols pharmacology, TOR Serine-Threonine Kinases genetics, Thiazoles chemistry, Antineoplastic Agents chemistry, Eukaryotic Initiation Factor-4A chemistry, Neoplasms drug therapy, Small Molecule Libraries chemistry, Sterols chemistry
- Abstract
The PI3K/Akt/mTOR kinase pathway is extensively deregulated in human cancers. One critical node under regulation of this signaling axis is eukaryotic initiation factor (eIF) 4F, a complex involved in the control of translation initiation rates. eIF4F-dependent addictions arise during tumor initiation and maintenance due to increased eIF4F activity-generally in response to elevated PI3K/Akt/mTOR signaling flux. There is thus much interest in exploring eIF4F as a small molecule target for the development of new anticancer drugs. The DEAD-box RNA helicase, eIF4A, is an essential subunit of eIF4F, and several potent small molecules (rocaglates, hippuristanol, pateamine A) affecting its activity have been identified and shown to demonstrate anticancer activity in vitro and in vivo in preclinical models. Recently, a number of new small molecules have been reported as having the capacity to target and inhibit eIF4A. Here, we undertook a comparative analysis of their biological activity and specificity relative to the eIF4A inhibitor, hippuristanol., (© 2020 Naineni et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
- Published
- 2020
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