INTRODUCTION: Tropomyosin receptor kinases (Trks) are a family of three similar 
tyrosine kinases activated by peptide hormones of the neurotrophin family. The 
nerve growth factor antibody tanezumab has provided clinical proof of concept 
for inhibition of the TrkA pathway in pain. As an alternative modality, 
small-molecule inhibitors of the Trks have been pursued in recent years to probe 
the role of these neurotrophin pathways in pain, cancer and other indications.
AREAS COVERED: This paper reviews the patent literature between mid-2009 and 
2013, claiming inhibitors of Trk family members as the primary biological 
targets. Additional patents have been reviewed where Trk is not the main kinase 
of interest but in which high Trk potency is observed and the chemical matter is 
particularly noteworthy. Patents pre-dating this period have been reviewed 
previously. Scifinder and Google were used to find relevant patents and clinical 
information using Trk or Tropomyosin as the search term.
EXPERT OPINION: Considerable recent progress has been made in the identification 
of selective pan Trk inhibitors with pharmacodynamic and pharmacokinetic 
properties appropriate for clinical evaluation. Inhibitors of both active and 
inactive conformations of the Trks as well as peripherally restricted molecules 
have been identified. Furthermore, TrkA-selective allosteric inhibitors have 
recently been disclosed, which enables the biology of this isoform to be probed. 
The recent identification of a TrkA gene fusion in a subset of lung cancer 
patients will increase further the attraction of Trk inhibition to the 
pharmaceutical industry.