BI 2536

Background

BI 2536 is a small molecule inhibitor of mammalian polo-like kinases (PLKs) with a strong selectivity for PLK1 (IC₅₀ = 0.83 nM) (1). PLK1 is important in regulating mitosis and is often overexpressed in cancers, contributing to excessive cell proliferation and loss of key checkpoint functions (1,2). Research indicates that BI 2536 causes mitotic arrest and apoptosis in 32 unique human cancer cell lines and inhibits the growth of human tumor xenografts in nude mice, with little to no effect on healthy cells (1,3). This along with the fact that BI 2536 exhibits high permeability through the blood-brain barrier, makes it an important therapeutic tool (4). BI 2536 inhibits BRD4 (IC₅₀ = 100 nM) and BRD4-dependent c-Myc expression in MM.1S multiple myeloma cells (5). Recently, BRD4 inhibition has shown anti-viral activity and increased host resistance to several DNA and RNA viruses, making BRD4 disruptors important compounds to study in relation to viral diseases (6).