A Pan-Specific Inhibitor of the Polo-Box Domains of Polo-like Kinases Arrests Cancer Cells in Mitosis

ChemBioChem, 2009, 10.1002/cbic.200900059, published on 04.02.2009
ChemBioChem, online article
Polo-like kinases (Plks) are a conserved family of serine/threonine kinases.[1, 2] The family member Plk1 is a key regulator of mitosis[1, 2] and has been identified as a negative prognostic marker for tumor patients.[3, 4] The widespread recognition of Plk1 as a therapeutic target for the treatment of human tumors has triggered numerous drug discovery programs.[5–16] The vast majority of Plk1 inhibitors are thought to act on the ATP-binding pocket of the enzyme.[6–16] Due to the conserved nature of the ATP-binding pocket in the family of protein kinases and other ATP-binding enzymes, the development of monospecific, ATP-competitive inhibitors is an enormous challenge.

TU München
Helmholtz München
MPI of Neurobiology
MPI of Biochemistry