BI-9564

BI-9564 is a potent, selective and cell-permeable BRD9/BRD7 bromodomains inhibitor, with IC₅₀s of 75 nM and 3.4 μM and K_ds of 14 nM and 239 nM, respectively. BI-9564 has an IC₅₀ of > 100 μM for BET family^[1]. IC50 & Target: Kd: 20 nM (BRD9) In Vitro: BI-9564 (<5 μM) shows no activity against 324 kinases, and at 10 μM, an inhibition >40% is observed for only 2 out of 55 GPCRs. BI-9564 has antiproliferative effect on human acute myeloid eosinophilic leukemia cell line EOL-1, with EC₅₀ of 800 nM^[1]. BI-9564 shows K_d of 73 nM for BRD7, and is >10-fold more selective for BRD9 over the highly homologues bromodomain BRD7, which has been implied as a tumor suppressor and is down-regulated in cancer cells^[2]. In Vivo: BI-9564 (180 mg/kg, p.o.) shows attractive ADME/PK profiles for in vivo proof-of-concept studies. BI-9564 results in a modest but significant additional survival benefit of 2 days compared to survival of the control group in a xenograft model of human AML^[1].