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

doi:10.1021/acs.jmedchem.8b01092

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

Pharmacology and Toxicology

Research output: Contribution to journal › Review article › peer-review

20 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 language	English (US)
Pages (from-to)	1731-1760
Number of pages	30
Journal	Journal of Medicinal Chemistry
Volume	62
Issue number	4
DOIs	https://doi.org/10.1021/acs.jmedchem.8b01092
State	Published - Feb 28 2019

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors : Development and Clinical Application. / Yan, Wei; Lakkaniga, Naga Rajiv; Carlomagno, Francesca; Santoro, Massimo; McDonald, Neil Q.; Lv, Fengping; Gunaganti, Naresh; Frett, Brendan; Li, Hong Yu.

In: Journal of Medicinal Chemistry, Vol. 62, No. 4, 28.02.2019, p. 1731-1760.

Research output: Contribution to journal › Review article › peer-review

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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.",

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AU - Santoro, Massimo

AU - McDonald, Neil Q.

AU - Lv, Fengping

AU - Gunaganti, Naresh

AU - Frett, Brendan

AU - Li, Hong Yu

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AB - 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.

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