LT-171-861, a novel FLT3 inhibitor, shows excellent preclinical efficacy for the treatment of FLT3 mutant acute myeloid leukemia.

ABSTRACT: Rationale: Acute myeloid leukemia (AML) is a common type of haematological malignancy. Several studies have shown that neoplasia in AML is enhanced by tyrosine kinase pathways. Recently, given that aberrant activation of Fms-like tyrosine receptor kinase 3 (FLT3) acts as a critical survival signal for cancer cells in 20‒30% patients with AML, inhibition of FLT3 may be a potential therapeutic strategy. Therefore, we identified LT-171-861, a novel kinase inhibitor with remarkable inhibitory activity against FLT3, in preclinical models of AML. Methods: We determined the inhibitory effects of LT-171-861 in vitro using AML cell lines and transformed BaF3 cells. Target engagement assays were used to verify the interaction between LT-171-861 and FLT3. Finally, a subcutaneous

SUBMITTER: Yu Z 

PROVIDER: S-EPMC7681098 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature