BI 2536 (755038-02-9) was originally reported as a potent (IC50’s Plk1 = 0.83nM, Plk2 = 3.5nM and Plk3 = 9.0nM)1?and selective2?Polo-like kinase inhibitor?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
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
