Biochemicals & reagents
1) Rudolph et al. (2009) BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity; Clin. Cancer Res. 15 3094 2) Rudolph et al. (2015) Efficacy and Mechanism of Action of Volasertib, a Potent and Selective Inhibitor of Polo-Like Kinases, in Preclinical Models of Acute Myeloid Leukemia; J. Pharmacol. Exp. Ther. 352 579 3) Ciceri et al. (2014) Dual kinase-bromodomain inhibitors for rationally designed polypharmacology; Nat. Chem. Biol. 10 305
Volasertib is an extremely potent and selective inhibitor (IC50’s: Plk1= 0.87 nM, Plk2 = 5 nM, Plk3 = 56 nM) of Polo-like kinase (1) which is a critical controller of multiple essential steps of mitosis (1). This compound has shown efficacy in multiple solid xenograft tumors models (1) and in clinical studies in patients with acute myeloid leukemia (2). It has also been shown to potently inhibit BRD43 (Kd = 79 nM3, IC50’s bromodomains 1 and 2 of BRD4 = 300 and 770 nM respectively (2).