Novel FLT3 tyrosine kinase inhibitors

Expert Opin Investig Drugs. 2003 Dec;12(12):1951-62. doi: 10.1517/13543784.12.12.1951.

Abstract

Acute myeloid leukaemia (AML) is an aggressive haematological malignancy that is curable in approximately 40% of cases. Activating mutations of the receptor tyrosine kinase FLT3 (FMS-like tyrosine kinase-3) are the single most common molecular abnormalities in AML and are associated with a distinctly worse prognosis. In an effort to target this mutation and improve outcomes in this subgroup of AML patients, several novel small-molecule FLT3 tyrosine kinase inhibitors are currently in development. Some of these FLT3 inhibitors are useful only as laboratory tools, while others clearly have clinical potential. These compounds are derived from a wide variety of chemical classes and differ significantly both in their potency and selectivity. This review summarises these developments and examines these novel agents with regard to both the assays used to characterise them and their clinical potential.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Mutation / genetics
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • fms-Like Tyrosine Kinase 3

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • FLT3 protein, human
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3