The use of kinase-directed precision medicine has been heavily pursued since the discovery and development of imatinib. Annually, it is estimated that around ∼20 000 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.
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. - ISSN 0022-2623. - 62:4(2019), pp. 1731-1760. [10.1021/acs.jmedchem.8b01092]
Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application
Carlomagno, Francesca;Santoro, Massimo;
2019
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 ∼20 000 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
