MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel

Mol Cancer Ther. 2010 Jan;9(1):157-66. doi: 10.1158/1535-7163.MCT-09-0609. Epub 2010 Jan 6.


Aurora-A kinase is a one of the key regulators during mitosis progression. Aurora-A kinase is a potential target for anticancer therapies because overexpression of Aurora-A, which is frequently observed in some human cancers, results in aberrant mitosis leading to chromosomal instability and possibly tumorigenesis. MK-5108 is a novel small molecule with potent inhibitory activity against Aurora-A kinase. Although most of the Aurora-kinase inhibitors target both Aurora-A and Aurora-B, MK-5108 specifically inhibited Aurora-A kinase in a panel of protein kinase assays. Inhibition of Aurora-A by MK-5108 in cultured cells induced cell cycle arrest at the G(2)-M phase in flow cytometry analysis. The effect was confirmed by the accumulation of cells with expression of phosphorylated Histone H3 and inhibition of Aurora-A autophosphorylation by immunostaining assays. MK-5108 also induced phosphorylated Histone H3 in skin and xenograft tumor tissues in a nude rat xenograft model. MK-5108 inhibited growth of human tumor cell lines in culture and in different xenograft models. Furthermore, the combination of MK-5108 and docetaxel showed enhanced antitumor activities compared with control and docetaxel alone-treated animals without exacerbating the adverse effects of docetaxel. MK-5108 is currently tested in clinical trials and offers a new therapeutic approach to combat human cancers as a single agent or in combination with existing taxane therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Aurora Kinase A
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / chemistry
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Docetaxel
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mitosis / drug effects
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Rats
  • Taxoids / pharmacology*
  • Taxoids / toxicity
  • Thiazoles / administration & dosage
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Xenograft Model Antitumor Assays


  • 4-(3-chloro-2-fluorophenoxy)-1-((6-(1,3-thiazol-2-ylamino)pyridin to 2-yl)methyl) cyclohexanecarboxylic acid
  • Antineoplastic Agents
  • Cyclohexanecarboxylic Acids
  • Protein Kinase Inhibitors
  • Taxoids
  • Thiazoles
  • Docetaxel
  • AURKB protein, human
  • Aurka protein, mouse
  • Aurka protein, rat
  • Aurkb protein, mouse
  • Aurkb protein, rat
  • Aurora Kinase A
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases