42816-53-5Relevant articles and documents
Discovery of an eIF4A Inhibitor with a Novel Mechanism of Action
Alimusa, Erin A.,Ambrose, Andrew J.,Buckley, Thomas M.,Chapman, Eli,Cunningham, Tyler A.,Dodson, Matthew,Essegian, Derek J.,Moore, Kohlson T.,Schürer, Stephan C.,Schatz, Jonathan H.,Shi, Taoda,Sivinski, Jared,Tulino, Allison S.,Wilson, Nathan C.,Zerio, Christopher J.,Zhang, Donna D.
, p. 15727 - 15746 (2021/11/13)
Increased protein synthesis is a requirement for malignant growth, and as a result, translation has become a pharmaceutical target for cancer. The initiation of cap-dependent translation is enzymatically driven by the eukaryotic initiation factor (eIF)4A, an ATP-powered DEAD-box RNA-helicase that unwinds the messenger RNA secondary structure upstream of the start codon, enabling translation of downstream genes. A screen for inhibitors of eIF4A ATPase activity produced an intriguing hit that, surprisingly, was not ATP-competitive. A medicinal chemistry campaign produced the novel eIF4A inhibitor 28, which decreased BJAB Burkitt lymphoma cell viability. Biochemical and cellular studies, molecular docking, and functional assays uncovered that 28 is an RNA-competitive, ATP-uncompetitive inhibitor that engages a novel pocket in the RNA groove of eIF4A and inhibits unwinding activity by interfering with proper RNA binding and suppressing ATP hydrolysis. Inhibition of eIF4A through this unique mechanism may offer new strategies for targeting this promising intersection point of many oncogenic pathways.
A Palladium-Catalyzed Double Carbonylation Approach to Isatins from 2-Iodoanilines
Laursen, Simon R.,Jensen, Mikkel T.,Lindhardt, Anders T.,Jacobsen, Mikkel F.,Skrydstrup, Troels
supporting information, p. 1881 - 1885 (2016/05/09)
A high-yielding procedure for the synthesis of isatins has been developed. Sequential Pd-catalyzed double carbonylation of 2-iodoanilines with near stoichiometric amounts of CO followed by acid-promoted cyclization readily affords an array of isatins. The conversion of 2-iodoanilines to isatins in good to excellent yields was found to proceed with good functional group tolerance. This protocol proved adaptable to 13C-isotope labeling of isatins, which was extended to the synthesis of the 13C-isotope labeled antiviral drug metisazone and the experimental anti-schizophrenia drug ML137.
PTEN INHIBITORS
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Page/Page column 77-78, (2008/06/13)
The therapeutic use of inhibitors of PTEN activity in the treatment of PTEN-mediated diseases, conditions, and injuries is disclosed.