BI-9564

IC50: 75 nM and 3.4 μM for BRD9 and BRD7 bromodomains, respectively

BI-9564 is a BRD9/7 specific inhibitor.

BRD7 and BRD9 are two important members of the bromodomain family protein. Both BRD7 and BRD9 have been implicated in chromatin remodeling.

In vitro: BI-9564 was identified as a BRD9/7 specific inhibitor via fragment-based screening and structure-guided design. BI-9564 was found to be bind to BRD9 with a higher affinity than to BRD7, and was negative on BET family proteins. In addition, BI-9564 demonstrated in vitro off-target selectivity to CECR2, but not in cells [1].

In vivo: In animal study, BomTac:NMRIFoxn1nu mice were given two oral doses daily and the concentration of BI-9564 in plasma was measured. Dose-dependent AUCs were obtained for BI-9564, achieving exposures that were higher compared to the EC50 level for EOL-1 cells. Moreover, when the oral treatment with BI-9564 at 180 mg/kg was initiated on day 5 and applied daily with an interruption at day 18 and 19, a significant reduction in tumour growth compared to controls was found on day 18 leading to a median tumour growth inhibition value of 52% [1].

Clinical trial: Up to now, BI-9564 is still in the preclinical development stage.

Reference:
[1] Martin LJ et al.  Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.