Trk kinase inhibitors as new treatments for cancer and pain.

ABSTRACT

BACKGROUND: Tropomyosin-related kinases (Trks) are a family of receptor tyrosine kinases activated by neurotrophins. Trks play important roles in pain sensation as well as tumour cell growth and survival signaling. Thus, inhibitors of Trk receptor kinases might provide targeted treatments for pain and cancer. OBJECTIVE: This paper reviews those patent applications since 2002 claiming small-molecule inhibitors of Trk receptor kinases. METHODS: Primary literature and patents were searched with SciFinder and Google Scholar. Patents were selected based on their relevance to Trks and were evaluated and representative compounds were listed as examples. RESULTS/CONCLUSION: Several series of Trk inhibitors with excellent in vitro potencies have been reported and a number of compounds have gone into the clinic. It should be noted that few of these inhibitors are Trk selective, demonstrating that targeting Trk kinases for treatment of pain and/or cancer offers a promising but also challenging approach.