Entrectinib

ROS Kinase|||ROS|||ALK|||Autophagy|||Trk receptor

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Entrectinib (RXDX-101) is a Trk, ROS1, and ALK inhibitor that inhibits TrkA, TrkB, TrkC, ROS1, and ALK (IC50=1/3/5/12/7 nM) with oral activity and blood-brain-barrier penetration. Entrectinib exhibits both antitumor and CNS activity.

Entrectinib is an inhibitor of TrkA (IC50 = 1.7 nM), TrkB (IC50 = 0.1 nM), and TrkC (IC50 = 0.1 nM), as well as C-ros oncogene 1 (ROS1; IC50 = 0.2 nM) and anaplastic lymphoma kinase (ALK; IC50 = 1.6 nM). Entrectinib blocks proliferation of ALK-dependent cell lines, including those with L1196M or C1156Y resistance mutations, and inhibits ALK?dependent signaling. It has been shown to inhibit the growth of a non-small cell lung Y cell line bearing an EML4-ALK rearrangement. In mice bearing various Trk, ROS1, or ALK-driven xenografts, entrectinib has been shown to induce tumor regression.