This federal Project Grant award from the National Cancer Institute (CFDA 93.395 Cancer Treatment Research) provides $738,024 to St. Jude Children's Research Hospital Inc. to develop high-quality chemical probes that can functionally annotate the chromatin binding domains within the epigenetic regulator BPTF in neuroblastoma. The goal is to assess BPTF's role in regulating oncogenic pathways involving MYC and MYCN, with the intent of establishing BPTF as a potential therapeutic target for this aggressive pediatric cancer. The award will fund the optimization of BPTF bromodomain and plant homeodomain (PHD) inhibitors, leveraging innovative structural biology methods. The resulting chemical probes will enable in-depth mechanistic studies to elucidate how BPTF's chromatin binding functions contribute to neuroblastoma pathogenesis, and may provide starting points for the development of new therapeutic candidates.