Biological Activity:

BI-9546 is a potent, selective and cell-permeable BRD9 inhibitor with IC50 ~75 nM (Alpha assay). It has good selectivity over BRD7 (IC50 ~3410 nM, Alpha assay). It has high selectivity against the other bromodomain family members (48 bromodomains) and kinases. In EOL-1 cellular proliferation assay, BI-9546 has IC50 at 800 nM. It has very good pharmacokinetic profiling, and also displays antitumor activity in EOL-1 AML xenograft model with oral treatment. BI-9546 could be a useful chemical tool to further explore BRD9 bromodomain biology in both in vitro and in vivo settings.

How to Use:

In vitro: BI-9546 was used at 1-10 µM in vitro and cellular assays.
In vivo: BI-9546 was orally dosed to mice in EOL-1 AML xenograft model at 180 mg/kg once per day.


Reference:

1. 1. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. (2016) J Med Chem. 59(10):4462-75.