NSC-19630

NSC-19630 (MIRA-1) is a cell-permeable inhibitor of Werner syndrome WRN helicase activity (IC₅₀ = 20 µM) over its ATPase and exonuclease activities, but did not affect other DNA helicases [Bloom syndrome (BLM), Fanconi anemia group J (FANCJ), RECQ1, RecQ, UvrD, or DnaB). Exposure of human cells to NSC 19630 dramatically impairs growth and proliferation, induces apoptosis in a WRN-dependent manner, and results in elevated γ-H2AX and proliferating cell nuclear antigen (PCNA) foci. NSC-19630 exposure leads to delayed S-phase progression, consistent with the accumulation of stalled replication forks, and to DNA damage in a WRN-dependent manner.