NanoBRET Tracer Development for Class I Bromodomain Target Engagement in Live Cells.

ABSTRACT: Epigenetic reader proteins, such as bromodomains, are often associated with diseases such as cancer and inflammation. BET bromodomain inhibitors have been studied extensively; however, non-BET bromodomains are understudied. Moreover, available high-throughput biological assays to assess inhibitors are limited. One non-BET bromodomain-containing protein, BPTF, has a recently reported inhibitor, BZ1, with an in vitro affinity of 6.3 nM. Additionally, BZ1 is known to be non-selective towards other class I bromodomains PCAF, GCN5, and CECR2. Here, we use a BZ1 analog, BZ1-THQ, to design a small molecule NanoBRET tracer, MS-1, for assessing inhibitor functional activity through live-cell target engagement against the BPTF bromodomain. Further, we investigate the versatility of MS-1

SUBMITTER: Sneddon MS 

PROVIDER: S-EPMC12697680 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature