BI 894999 is a potent and selective BET inhibitor with IC50 of 5 nM and 41 nM for the binding of BRD4-BD1 and BRD4-BD2 to acetylated histones, respectively. BI 894999 is highly selective for BRD2/3/4 and BRDT (Kd of 0.49-1.6?nM), with at least a 200-fold selectivity vs. BRD4-BD1.
BI 894999 is highly active in AML cell lines, primary patient samples. BI 894999 targets super-enhancer-regulated oncogenes and other lineage-specific factors, which are involved in the maintenance of the disease state. [1]
BI 894999 is active as monotherapy in AML xenografts, and in addition leads to strongly enhanced antitumor effects in combination with CDK9 inhibitors. [1]
[1] Daniel Gerlach, et al. Oncogene. 2018 May;37(20):2687-2701. [2] Ulrike Tontsch-Grunt, et al. Cancer Lett. 2018 May 1;421:112-120.