Entrectinib: a potent new TRK, ROS1, and ALK inhibitor.

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Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, Giallombardo M, Peeters M, Raez L

Entrectinib: a potent new TRK, ROS1, and ALK inhibitor.

Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12.

PubMed ID

26457764 [ View in PubMed

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Abstract

INTRODUCTION: Receptor tyrosine kinases (RTKs) and their signaling pathways, control normal cellular processes; however, their deregulation play important roles in malignant transformation. In advanced non-small cell lung cancer (NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the development of molecularly targeted agents that only benefit roughly 20% of patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent anti-neoplastic activity and tolerability in various neoplastic conditions, particularly NSCLC. AREAS COVERED: This review outlines the pharmacokinetics, pharmacodynamics, mechanism of action, safety, tolerability, pre-clinical studies and clinical trials of entrectinib, a promising novel agent for the treatment of advanced solid tumors with molecular alterations of Trk-A, B and C, ROS1 or ALK. EXPERT OPINION: Among the several experimental drugs under clinical development, entrectinib is emerging as an innovative and promising targeted agent. The encouraging antitumor activity reported in the Phase 1 studies, together with the acceptable toxicity profile, suggest that entrectinib, thanks to its peculiar mechanism of action, could play an important role in the treatment-strategies of multiple TRK-A, B, C, ROS1, and ALK- dependent solid tumors, including NSCLC and colorectal cancer. That being said, further evidence for its clinical use is still needed.

DrugBank Data that Cites this Article

Drugs

Entrectinib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Entrectinib	BDNF/NT-3 growth factors receptor	Protein	Humans	Unknown	Inhibitor	Details
Entrectinib	High affinity nerve growth factor receptor	Protein	Humans	Yes	Inhibitor	Details
Entrectinib	NT-3 growth factor receptor	Protein	Humans	Yes	Inhibitor	Details
Entrectinib	Proto-oncogene tyrosine-protein kinase ROS	Protein	Humans	Yes	Inhibitor	Details