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AOH1996 is an inhibitor of proliferating cell nuclear antigen (PCNA).1 It binds to PCNA in a thermal shift assay. AOH1996 (500 nM) induces apoptosis in SK-N-DZ neuroblastoma cells but not 7SMOO32 normal neural crest stem cells. It induces DNA damage in SK-N-AS neuroblastoma cells expressing wild-type DNA-directed RNA polymerase II subunit RPB1 but not in SK-N-AS cells expressing RPB1Y418A. AOH1996 (40 mg/kg) decreases tumor volume in SK-N-BE(2)-C neuroblastoma, MDA-MB-468 breast cancer, and NCI H82 small cell lung cancer mouse xenograft models.
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1. Small molecule targeting of transcription-