eIF4A3-IN-1

eIF4A3-IN-1 (Compound 53a) is a highly selective, cell-active inhibitor of eukaryotic initiation factor 4A3 (eIF4A3), exhibiting an ATPase IC50 of 0.26 µM and a KD of 0.043 µM. By directly binding a non-ATP site on eIF4A3, eIF4A3-IN-1 inhibits RNA-dependent ATPase activity while demonstrating excellent selectivity over related helicases eIF4A1, eIF4A2, DHX29, and BRR2 (all IC50 >100 µM). This targeted inhibition subsequently causes dose-dependent cellular suppression of nonsense-mediated RNA decay (NMD), affecting the stability of mRNAs with premature termination codons.