Home
Resources
Publications
GSK2801, a BAZ2/BRD9 Bromodomain Inhibitor, Synergizes With BET Inhibitors to Induce Apoptosis in Triple-Negative Breast Cancer

GSK2801, a BAZ2/BRD9 Bromodomain Inhibitor, Synergizes With BET Inhibitors to Induce Apoptosis in Triple-Negative Breast Cancer

Samantha M Bevill, Jose F Olivares-Quintero, Noah Sciaky, Brian T Golitz, Darshan Singh, Adriana S Beltran, Naim U Rashid, Timothy J Stuhlmiller, Andrew Hale, Nathaniel J Moorman, Charlene M Santos, Steven P Angus, etc.

Mol Cancer Res. 2019 Jul;17(7):1503-1518.

PMID: 31000582

Abstract:

Screening of an inhibitor library targeting kinases and epigenetic regulators identified several molecules having antiproliferative synergy with extraterminal domain (BET) bromodomain (BD) inhibitors (JQ1, OTX015) in triple-negative breast cancer (TNBC). GSK2801, an inhibitor of BAZ2A/B BDs, of the imitation switch chromatin remodeling complexes, and BRD9, of the SWI/SNF complex, demonstrated synergy independent of BRD4 control of P-TEFb-mediated pause-release of RNA polymerase II. GSK2801 or RNAi knockdown of BAZ2A/B with JQ1 selectively displaced BRD2 at promoters/enhancers of ETS-regulated genes. Additional displacement of BRD2 from rDNA in the nucleolus coincided with decreased 45S rRNA, revealing a function of BRD2 in regulating RNA polymerase I transcription. In 2D cultures, enhanced displacement of BRD2 from chromatin by combination drug treatment induced senescence. In spheroid cultures, combination treatment induced cleaved caspase-3 and cleaved PARP characteristic of apoptosis in tumor cells. Thus, GSK2801 blocks BRD2-driven transcription in combination with BET inhibitor and induces apoptosis of TNBC. IMPLICATIONS: Synergistic inhibition of BDs encoded in BAZ2A/B, BRD9, and BET proteins induces apoptosis of TNBC by a combinatorial suppression of ribosomal DNA transcription and ETS-regulated genes.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4246389	GSK2801			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: