https://www.selleckchem.com/products/cathepsin-g-inhibitor-i.html Dysregulation of protein translation is a key driver for the pathogenesis of many cancers. Eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase, is a critical component of the eIF4F complex, which regulates cap-dependent protein synthesis. The flavagline class of natural products (i.e., rocaglamide A) has been shown to inhibit protein synthesis by stabilizing a translation-incompetent complex for select messenger RNAs (mRNAs) with eIF4A. Despite showing promising anticancer phenotypes, the development of flavagline derivatives as therapeutic agents has been hampered because of poor drug-like properties as well as synthetic complexity. A focused effort was undertaken utilizing a ligand-based design strategy to identify a chemotype with optimized physicochemical properties. Also, detailed mechanistic studies were undertaken to further elucidate mRNA sequence selectivity, key regulated target genes, and the associated antitumor phenotype. This work led to the design of eFT226 (Zotatifin), a compound with excellent physicochemical properties and significant antitumor activity that supports clinical development.Two shape-persistent arylene ethynylene macrocycles have been designed and synthesized as scaffolds to bind the nonpolar molecule 1,4-diiodobutadiyne. Binding via halogen bonding interactions between the pyridine moieties of the macrocycle and 1,4-diiodobutadiyne is predicted by density functional theory calculations and has been demonstrated in solution by 13C NMR titrations. The binding constant for the macrocycle-monomer complex (K = 10.5 L mol-1) is much larger than for other comparable halogen bonds, strongly supporting cooperative binding of both ends of the diyne. These results demonstrate a fully inserted geometry of 1,4-diiodobutadiyne in the complex.Recent advances have led to numerous landmark discoveries of [4Fe4S] clusters coordinated by essential enzymes in r