A Comparative Study of Small Molecules Targeting eIF4A.

A Comparative Study of Small Molecules Targeting eIF4A. RNA. 2020 Feb 03;: Authors: Naineni SK, Itoua Maiga R, Cencic R, Putnam AA, Amador LA, Rodriguez AD, Jankowsky E, Pelletier J 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 anti-cancer 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 anti-cancer activity in vitro and in vivo in pre-clinical 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. PMID: 32014999 [PubMed - as supplied by publisher]
Source: RNA - Category: Genetics & Stem Cells Authors: Tags: RNA Source Type: research