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Helicase inhibitors act on the enzymes that unwind DNA and RNA duplexes during replication and repair. Helicases use adenosine triphosphate (ATP) to separate nucleic acid strands, which gives repair and recombination machinery access to single strands. Cancer cells with microsatellite instability were found in 2019 to depend on the Werner syndrome helicase (WRN), and expanded thymine-adenine (TA) dinucleotide repeats were later linked to that dependence. The list reflects this focus with WRN inhibitors such as VVD-214 and NSC 617145. Related RecQ family enzymes are covered by BLM-IN-2 against the Bloom syndrome helicase (BLM) and by RECQL5-IN-1. DHX9-IN-1 acts on the RNA helicase DExH-box helicase 9 (DHX9), which resolves R-loops and other structured nucleic acids.
