BI 2536
Dual Plk/BRD4 inhibitor - Destabilizes Myc / BI 2536 was originally reported as a potent (IC50’s Plk1 = 0.83nM, Plk2 = 3.5nM and Plk3 = 9.0nM) and selective2 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
Biochemicals & reagents
755038-02-9
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
-20°C
TARGET: Bromodomain -- PATHWAY: Chromatin; Posttranslational modification; Cell cycle; Apoptosis inducer; Myc -- RESEARCH AREA: Epigenetics; Ubiquitin/Proteasome; Cell death -- DISEASE AREA: Cancer