In rat and monkey models, Larotrectinib (LOXO-101) exhibits oral bioavailability ranging from 33% to 100% and plasma protein binding between 60% and 65%. It displays minimal brain penetration and demonstrates good tolerance in 28-day GLP toxicology assessments. A single administration of Larotrectinib (LOXO-101) at a dose of 30 mg/kg reduces tyrosine phosphorylation of TRKA and downstream signal transduction (pERK) in tumors by over 80%^[1].

Athymic nude mice inoculated with KM12 cells receive daily oral doses of Larotrectinib (LOXO-101) for two weeks. The treatment results in dose-dependent inhibition of tumor growth, indicating the efficacy of this selective compound in suppressing tumor growth in vivo ^[4].

Larotrectinib (LOXO-101) (200mg/kg/day, pO for six weeks) leads to the elimination of leukemic infiltration in the bone marrow and spleen, compared to mice treated with the vehicle alone. Even four weeks after the treatment is stopped, mice receiving Larotrectinib (LOXO-101) remain alive and free from leukemia, as confirmed by Xenogen imaging^[5].

Larotrectinib (LOXO-101) is an ATP-competitive oral inhibitor targeting the tropomyosin-related kinase (TRK) family of receptor kinases (TRKA, B, and C). It exhibits low nanomolar 50% inhibitory concentrations against all three isoforms and demonstrates 1,000-fold or greater selectivity relative to other kinases^[1][2].

Assessment of cell proliferation post-treatment with Larotrectinib (LOXO-101) reveals a dose-dependent suppression across all three cell lines. The IC50 values are below 100 nM for CUTO-3.29 and below 10 nM for KM12 and MO-91, aligning with the established potency of this drug against the TRK kinase family^[3].