Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application

Wei Yan, Naga Rajiv Lakkaniga, Francesca Carlomagno, Massimo Santoro, Neil Q. McDonald, Fengping Lv, Naresh Gunaganti, Brendan Frett, Hong Yu Li

Research output: Contribution to journalReview article

10 Scopus citations

Abstract

The use of kinase-directed precision medicine has been heavily pursued since the discovery and development of imatinib. Annually, it is estimated that around 20000 new cases of tropomyosin receptor kinase (TRK) cancers are diagnosed, with the majority of cases exhibiting a TRK genomic rearrangement. In this Perspective, we discuss current development and clinical applications for TRK precision medicine by providing the following: (1) the biological background and significance of the TRK kinase family, (2) a compilation of known TRK inhibitors and analysis of their cocrystal structures, (3) an overview of TRK clinical trials, and (4) future perspectives for drug discovery and development of TRK inhibitors.

Original languageEnglish (US)
Pages (from-to)1731-1760
Number of pages30
JournalJournal of Medicinal Chemistry
Volume62
Issue number4
DOIs
StatePublished - Feb 28 2019

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Yan, W., Lakkaniga, N. R., Carlomagno, F., Santoro, M., McDonald, N. Q., Lv, F., Gunaganti, N., Frett, B., & Li, H. Y. (2019). Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application. Journal of Medicinal Chemistry, 62(4), 1731-1760. https://doi.org/10.1021/acs.jmedchem.8b01092