Utatrectinib (AZD-7451) is a potent, selective and orally active Trk inhibitor. Utatrectinib blocks TrkC activation and associated tumorigenic behaviors.
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].
Utatrectinib (50 mg/kg, p.o., daily) suppresses adenoid cystic carcinoma (ACC) tumor growth in ACCX6 xenograft nu/nu mice model[2].
References:
[1]. Kozaki R, et al. Combined use of Trk inhibitor containing heterocyclic urea derivative, and other kinase inhibitor for treating cancer. WO2019049891 A1. [2]. Ivanov SV, et al. TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior. Oncogene. 2013 Aug 8;32(32):3698-710.
[3]. Tatematsu T, et al. Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic tyrosine kinase receptor family expression in non-small-cell lung cancer and sensitivity to AZD7451 in vitro. Mol Clin Oncol. 2014 Sep;2(5):725-730.