FEN1-inhibitor co-crystal structure published

Mark Abbott has recently co-authored a paper in Nature Chemical Biology  as part of a collaboration between AstraZeneca, University of Sheffield and Pelago BioSciences. The publication describes the co-crystal structure of flap endonuclease 1 (FEN1) bound with small molecule inhibitors and describes how its function can be inhibited to provide clues for future drug discovery. Higher levels of FEN1 have been seen in cancer types associated with poor prognosis, potentially as a result of these cancer cells being reliant on this repair enzyme in the absence of other supporting DDR proteins. This over reliance on FEN1 repair means the cells become sensitive and die when FEN1 is blocked – a term called synthetic lethality. Preventing the action of enzymes like FEN1 may be a way of selectively killing such cancer cells as a new therapeutic class of anti-cancer agents.