207Pleasant St. SE, Department of Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
207Pleasant St. SE, Department of Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Curr Opin Chem Biol. 2021 Aug;63:57-67. doi: 10.1016/j.cbpa.2021.02.003. Epub 2021 Mar 8.
Nucleosome remodeling provides access to genomic DNA for recruitment of the transcriptional machinery to mediate gene expression. The aberrant function of nucleosome remodeling complexes has been correlated to human cancer, making them emerging therapeutic targets. The bromodomain PHD finger transcription factor, BPTF, is the largest member of the human nucleosome remodeling factor NURF. Over the last five years, BPTF has become increasingly identified as a protumorigenic factor, prompting investigations into the molecular mechanisms associated with BPTF function. Despite a druggable bromodomain, small molecule discovery is at an early stage. Here we highlight recent investigations into the biology being discovered for BPTF, chemical biology approaches used to study its function, and small molecule inhibitors being designed as future chemical probes and therapeutics.
核小体重塑为转录机制募集到基因组 DNA 提供了途径，从而介导基因表达。核小体重塑复合物的异常功能与人类癌症相关，使其成为新兴的治疗靶点。溴结构域 PH 结构域转录因子 BPTF 是人类核小体重塑因子 NURF 中最大的成员。在过去的五年中，BPTF 已越来越被确定为致癌因子，促使人们对与 BPTF 功能相关的分子机制进行研究。尽管存在可成药的溴结构域，但小分子药物的发现仍处于早期阶段。在这里，我们重点介绍了目前对 BPTF 的生物学研究、用于研究其功能的化学生物学方法，以及作为未来化学探针和治疗药物设计的小分子抑制剂。
