Larotrectinib sulfate (LOXO-101; ARRY-470)

Description: Larotrectinib sulfate (LOXO-101; ARRY-470; Vitrakvi) is a potent, oral, selective, ATP competitive TRK inhibitor with IC50s in low nanomolar range (2 to 20 nM) for inhibition of all TRK family members in binding and cellular assays. It has 100x selectivity over other kinases, and is with 2 to 20 nM cellular potency against the TRKA, TRKB, and TRKC kinases. LOXO-101 was evaluated for off-target kinase enzyme inhibition against a panel of non-TRK kinases at a concentration of 1, 000 nM and ATP concentrations around the Km. Preclinical models of LOXO-101 using TRK-fusion-bearing human-derived cancer cell lines demonstrate inhibition of the fusion oncoprotein and cellular proliferation in vitro, and tumor growth in vivo. On November 26, 2018, Larotrectinib was approved by the FDA, after having been initially awarded orphan drug status in 2015 for soft tissue sarcoma and breakthrough therapy designation in 2016 for the treatment of metastatic solid tumors with NTRK fusion. The approval was unusual in that it was only the second agent approved not for use with cancers of specific tissues, but rather for any tissue carrying specific mutations (i.e. the approval is 'tissue agnostic').

References: Mol Pain. 2010 Dec 7; 6:87. doi: 10.1186/1744-8069-6-87; Nat Med. 2013 Nov; 19(11):1469-72.

Related CAS#: 1223403-58-4 (free base); 1223405-08-0 (sulfate)

Publications Citing Use of InvivoChem Larotrectinib (LOXO-101; ARRY-470): Cell. 2020 Nov 25; 183(5):1202-1218.e25. doi: 10.1016/j.cell.2020.10.016.