Entrectinib

Entrectinib (NMS-E628) is an orally active, BBB-penetrated and centrally active inhibitor of TrkA/B/C, ROS1 and ALK, with IC₅₀ values of 1, 3, 5, 12 and 7 nM, respectively. Entrectinib induces apoptosis and cycle arrest in cancer cells, has antitumor activity, and attenuates bleomycin-induced lung fibrosis in mice^[1][2][3]. IC50 & Target:IC50: 1 nM (TrkA), 3 nM (TrkB), 5 nM (TrkC), 12 nM (ROS1), 7 nM (ALK)^[2]. In Vitro:Entrectinib (100, 200, 400 nM; 24 h) alleviates TGF-β1-induced activation of mouse lung fibroblasts^[1].
Entrectinib(100, 200, 400 nM; 24 h) inhibits TGF-β1-induced epithelial to mesenchymal transition of mouse lung epithelial cells^[1].
Entrectinib (10, 50, 250 nM; 2 h) abolishes autophosphorylation of TPM3-TRKA, concomitant with complete inhibition of the phosphorylation of PLCg1, AKT, and MAPK in KM12 cells^[2].
Entrectinib (10, 50, 250 nM; 24, 48 h) induce KM12 cells cycle arrest (24 h) and apoptosis (48 h)^[2]. In Vivo:Entrectinib (20, 40, 60 mg/kg; i.g.; single daily for 7 days) attenuates bleomycin-induced pulmonary fibrosis in mice^[1].
Entrectinib (30, 60 mg/kg; p.o.; twice daily for 10 consecutive days) induces regression of xenograft tumors in tumor-bearing mice, including TRKA-dependent colorectal cancer KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including brain-localized lung model cancer metastasis^[2].