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Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part II

Justin J Bailey1, Ralf Schirrmacher1, Kristen Farrell1

  • 1a Faculty of Medicine & Dentistry, Department of Oncology , University of Alberta , Edmonton , Canada.

Expert Opinion on Therapeutic Patents
|March 9, 2017
PubMed
Abstract

Insights

Trk inhibitors show promise for treating cancers and chronic pain, with ongoing research into new drug classes. Careful consideration of blood-brain barrier penetration is crucial to mitigate potential central nervous system side effects.

Area of Science:

  • Neuroscience
  • Oncology
  • Pharmacology

Background:

  • Tropomyosin receptor kinase (Trk) receptor activation is vital for neuronal development and function.
  • Dysregulation of Trk signaling is implicated in various human diseases, including cancer and chronic pain.
  • Trk inhibitors are emerging as a significant therapeutic strategy in oncology and neurology.

Purpose of the Study:

  • To review recent patent literature and clinical research on Trk family inhibitors.
  • To discuss the evolution of structurally diverse Trk inhibitors.
  • To highlight the therapeutic potential and challenges of Trk inhibitors in clinical applications.

Main Methods:

  • Review of patent literature concerning Trk inhibitors.
  • Analysis of clinical research data for Trk inhibitors.
  • Discussion of drug development strategies, including scaffold hopping and high-throughput screening (HTS).

Main Results:

  • Substantial growth in the number of structural classes and industrial entrants for Trk inhibitors over the past six years.
  • Increasing clinical investigations of Trk inhibitors, particularly for NTRK-fusion positive cancers and chronic pain.
  • Identification of Trk inhibitors' potential for adverse central nervous system (CNS) side effects.

Conclusions:

  • Trk inhibitors have evolved significantly, offering diverse structural classes for therapeutic targeting.
  • Clinical applications are expanding, especially in oncology and pain management.
  • Future drug development must rigorously consider blood-brain barrier (BBB) permeation to optimize safety and efficacy.
Keywords:
LOXO-101NTRK1/2/3TrkATrkBTrkCTropomyosin receptor kinasecancer treatmentchronic painentrectiniboncologypruritistargeted therapytropomyosin receptor kinase inhibitor

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