Table 1.

Summary of the mechanism of action, targets, pharmaceutical effects, and clinical trial results of first-generation and second-generation NTRK inhibitors, including larotrectinib, repotrectinib, or entrectinib

Aspect	Larotrectinib	Entrectinib	Repotrectinib
FDA approval year	November 26, 2018	August 15, 2019	November 15, 2023
Mechanism of action	Inhibits TRK fusion proteins, disrupting downstream signaling pathways	Blocks TRK fusion proteins,disrupting aberrant signaling cascade	Targets TRK fusion proteins, ROS1, and ALK, inhibiting signaling pathways
Targets	TRKA/B/C fusion proteins	TRK A/B/C fusion proteins, ROS1, ALK	TRKA/B/C fusion proteins, ROS1, ALK
Binding site	ATP-binding site (Type 1 kinase inhibitor)	ATP-binding site (Type 1 kinase inhibitor)	Allosteric binding site (Type 3 kinase inhibitor)
Pharmaceutical effects	Induces tumour regression in NTRK fusion-positive cancers	Exhibits efficacy in NTRK fusion-positive cancers	Active against NTRK, ROS1, and ALK-positive cancers
Clinical trial results	Demonstrates high response rates in clinical trials	Showed effectiveness in various cancer types	Demonstrates promising activity in clinical trials