Utatrectinib

Utatrectinib (AZD-7451) is a potent, selective and orally active Trk inhibitor. Utatrectinib blocks TrkC activation and associated tumorigenic behaviors[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Trk Receptor

Utatrectinib (100 nM, 22 h) inhibits the migration of TrkC-expressing U2SO cells[2]. Utatrectinib (1-10 nM, 24 h) inhibits cell growth in KM12, H460 and H810 cells[3]. Utatrectinib (5 nM, 24 h) inhibits phosphorylation of TRKA/B and downstream signaling in KM12, H460 cells[3]. Cell Migration Assay [2] Cell Line: TrkC-expressing U2SO cells Concentration: 100 nM Incubation Time: 22 h Result: Inhibited cell migration (~2.3-fold, P<0.01). Western Blot Analysis[3] Cell Line: KM12, H460 cells Concentration: 0, 1, 5 nM Incubation Time: 24 h Result: Inhibited pTRKA Tyr490 and pAk in KM12 cells. Inhibited pTRKB Tyr706/707 and pERK in H460 cells.

Utatrectinib (50 mg/kg, p.o., daily) suppresses adenoid cystic carcinoma (ACC) tumor growth in ACCX6 xenograft nu/nu mice model[2]. Animal Model: Xenograft nu/nu mice models of human ACC: ACCX6 and ACCX9[2] Dosage: 50 mg/kg Administration: Oral administration, daily. Result: Tumor growth inhibition (TGI): 64% (in ACCX6 model)