Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1)

Bioorg Med Chem Lett. 2013 Jun 15;23(12):3662-6. doi: 10.1016/j.bmcl.2013.02.083. Epub 2013 Feb 27.

Abstract

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.

Publication types

  • Clinical Trial, Phase I
  • Letter

MeSH terms

  • 4-Aminobenzoic Acid / chemistry
  • 4-Aminobenzoic Acid / pharmacokinetics
  • 4-Aminobenzoic Acid / pharmacology
  • Administration, Oral
  • Adult
  • Azepines / chemistry*
  • Azepines / pharmacokinetics
  • Azepines / pharmacology*
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Line, Tumor
  • Drug Discovery
  • Humans
  • Polo-Like Kinase 1
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Young Adult

Substances

  • 4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido(4,5-b)(1,4)diazepin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide
  • Azepines
  • Cell Cycle Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • 4-Aminobenzoic Acid