Dawn of Aurora kinase inhibitors as anticancer drugs

Expert Opin Investig Drugs. 2004 Sep;13(9):1199-201. doi: 10.1517/13543784.13.9.1199.

Abstract

With the current standard chemotherapy regimens only approximately 25% of acute myelogenous leukaemia (AML) patients survive > 5 years. Aurora kinases are overexpressed in many human cancers. VX-680 inhibited Aurora-A, -B, -C and the FMS-like tyrosine kinase-3 with apparent inhibitory constants of 0.6, 18, 4.6 and 30 nM, respectively. In primary leukaemia cells from patients with AML, which were refractory to standard therapies, VX-680 inhibited colony formation. In nude mice, VX-680 markedly reduced human AML tumours. The development of VX-680 for use in AML should continue.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aurora Kinase A
  • Aurora Kinases
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / pharmacology*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • 4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline
  • Antineoplastic Agents
  • Benzamides
  • Enzyme Inhibitors
  • Indoles
  • Piperazines
  • Quinazolines
  • Sulfonamides
  • VX680
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • hesperadin