zotatifin

Zotatifin is a first-in-class, potent and sequence-selective small molecule inhibitor of the RNA helicase eukaryotic initiation factor 4A (eIF4A). By stabilizing a ternary complex with eIF4A and mRNA at specific polypurine motifs within the 5’-UTR of select transcripts, zotatifin prevents ribosome docking and translation initiation for oncogenic drivers such as ERBB2 (HER2), FGFR1/2, EGFR, KRAS, CCND1 (Cyclin D1), androgen receptor (AR), HIF1A, and others. This results in downregulation of proteins critical for tumor growth and survival across multiple solid tumor types. Zotatifin also modulates the tumor immune microenvironment by repolarizing macrophages toward an M1-like phenotype and inhibiting neutrophil infiltration. It is being developed primarily for advanced solid tumors including breast cancer (ER+), non-small cell lung cancer (NSCLC), prostate cancer, pancreatic cancer, and other malignancies driven by aberrant translation or overexpression of these oncogenes[1][2][5][6][7][8].

Other names

zotatifin