BI-2536

BI 2536 was originally reported as a potent (IC50’s Plk1 = 0.83nM, Plk2 = 3.5nM and Plk3 = 9.0nM) and selective [2]. Polo-like kinase inhibitor (IC50’s Plk1 = 0.83nM, Plk2 = 3.5nM and Plk3 = 9.0nM) that caused mitotic arrest and apoptosis induction in various human cancer cell lines [1]. It was later found to be a potent inhibitor (IC50 = 100nM) of BET family member BRD4 and able to potently suppress c-Myc expression in MM.1S multiple myeloma cells [3]. BI 2536 destabilizes N-Myc by inhibiting the deactivation of the ubiquitin E3 ligase Fbw7 by Plk1 [4].

References:

1) Steegmaier et al. (2007), BI 2536, a Potent and Selective Inhibitor of Polo-like Kinase 1, Inhibits Tumor Growth In Vivo; Curr.Biol., 17 316

2) Davis et al. (2011), Comprehensive analysis of kinase inhibitor selectivity; Nat.Biotechnol., 29 1046

3) Ciceri et al. (2014), Dual kinase-bromodomain inhibitors for rationally designed polypharmacology; Nat.Chem.Biol., 10 305

4) Xiao et al. (2016), Polo-like Kinase-1 Regulates Myc Stabilization and Activates a Feedforward Circuit Promoting Tumor Cell Survival; Mol.Cell, 64 493