Aggarwal, Monika published the artcileInhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress, Formula: C8H9NO4, the main research area is Werner syndrome helicase inhibitor NSC19630 topotecan synergism antitumor.
Modulation of DNA repair proteins by small mols. has attracted great interest. An in vitro helicase activity screen was used to identify mols. that modulate DNA unwinding by Werner syndrome helicase (WRN), mutated in the premature aging disorder Werner syndrome. A small mol. from the National Cancer Institute Diversity Set designated NSC 19630 [1-(propoxymethyl)-maleimide] was identified that inhibited WRN helicase activity 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 impaired growth and proliferation, induced apoptosis in a WRN-dependent manner, and resulted in elevated γ-H2AX and proliferating cell nuclear antigen (PCNA) foci. NSC 19630 exposure led to delayed S-phase progression, consistent with the accumulation of stalled replication forks, and to DNA damage in a WRN-dependent manner. Exposure to NSC 19630 sensitized cancer cells to the G-quadruplex-binding compound telomestatin or a poly(ADP ribose) polymerase (PARP) inhibitor. Sublethal dosage of NSC 19630 and the chemotherapy drug topotecan acted synergistically to inhibit cell proliferation and induce DNA damage. The use of this WRN helicase inhibitor mol. may provide insight into the importance of WRN-mediated pathway(s) important for DNA repair and the replicational stress response.
Proceedings of the National Academy of Sciences of the United States of America published new progress about Antitumor agents. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Formula: C8H9NO4.
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