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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Entrectinib: A New Selective Tyrosine Kinase Inhibitor Approved for the Treatment of Pediatric and Adult Patients with NTRK Fusionpositive, Recurrent or Advanced Solid Tumors

Author(s): Hind M. Osman and Meral Tuncbilek*

Volume 29, Issue 15, 2022

Published on: 01 April, 2022

Page: [2602 - 2616] Pages: 15

DOI: 10.2174/0929867328666210914121324

Price: $65


Background: Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. It was developed by Roche and initially approved in Japan in 2019 to treat pediatric and adult patients with NTRK fusionpositive, recurrent, or advanced solid tumors. In August 2019, entrectinib received accelerated approval by the U.S FDA for this indication. It is also the first FDA-approved drug designed to target both NTRK and ROS1.

Objective: We aim to summarize recent studies related to the synthesis, mechanism of action, and clinical trials of the newly approved selective tyrosine kinase inhibitor entrectinib.

Methods: We conduct a literature review of the research studies on the new highly-potent small-molecule entrectinib.

Conclusion: Entrectinib, based on three clinical studies (ALKA, STARTRK-1, and STARTRK-2), was well tolerated, with a manageable safety profile. It induced clinically meaningful responses in recurrent or advanced solid tumors associated with NTRK fusion- positive or ROS1+ NSCLC. It demonstrated substantial efficacy in patients with CNS metastases.

Keywords: Entrectinib, indazol benzamide, Trk ABC, ALK, ROS1 inhibitor, NTRK fusion-positive tumors.

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