FEN1 inhibitor

FEN1 inhibitors are a class of targeted small molecule therapeutics designed to inhibit Flap Endonuclease 1 (FEN1), a structure-specific nuclease essential for DNA replication and repair. FEN1 plays a critical role in the removal of 5' flaps during Okazaki fragment maturation and long-patch base excision repair. By blocking FEN1 activity, these inhibitors induce replication stress and DNA damage, leading to genomic instability and cell death. This mechanism is particularly potent in cancers characterized by high baseline replication stress, such as MYCN-amplified neuroblastoma, or those with defects in other DNA repair pathways (e.g., BRCA1/2 deficiency), representing a synthetic lethal approach. Preclinical data presented at AACR 2026 demonstrates that FEN1 inhibition significantly reduces cell growth and viability in MYCN-amplified neuroblastoma models by triggering apoptosis and replication stress responses.

Other names

flap endonuclease 1 inhibitorFEN-1 inhibitorFEN1 inhibitorFEN 1 inhibitor