Larotrectinib sulfate (LOXO-101 sulfate) is an oral active and specific ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).

Larotrectinib is a specific kinase inhibitor with nanomolar activity against TRKA/TRKB/TRKC but no other notable kinase inhibition (1 μM). Larotrectinib hasn't the inhibitory of the proliferation of Ba/F3 cells expressing other oncogene targets (EGFR, ROS1 or ALK) or of lung and colorectal cell lines that do not harbor an NTRK1 fusion. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.

Early/sustained but not late/acute administration of ARRY-470(LOXO-101) obviously attenuates bone cancer pain and blocks the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor-bearing bone, but no significant inhibition for tumor growth or bone remodeling. It has very limited ability crossing of the blood-brain barrier.

Concentrations: 10,100,1000 nM. Method: Ba/F3 cells expressing MPRIP-NTRK1 (RIP-TRKA) or EV were lysed after 5 h of treatment with the indicated doses of drugs (ARRY-470; G,gefitinib 1,000 nM) or DMSO control.The cell lysate is used for western blot analysis.

Animal Models: Adult male C3H/HeJ mice. Formulation: Labrafac; polygly-colyzed glyceride. Dosages: 10-100 mg/kg. Administration: p.o.