GZD824 as a FLT3, FGFR1 and PDGFRα Inhibitor Against Leukemia In Vitro and In Vivo.

ABSTRACT: GZD824 is a novel third-generation BCR-ABL inhibitor. It entered Phase II clinical trials in China and Phase Ib clinical trials in USA in 2019 for treatment of patients with resistant chronic myeloid leukemia (CML). We found that at concentrations below 10 nM, GZD824 significantly suppresses FLT3, FGFR1 and PDGFRα kinase activities and inhibits their signal pathways in MV4-11^Flt3-ITD, KG-1^{FGFR1OP2-FGFR1} and EOL-1^{FIP1L1-PDGFRa} leukemia cells. It selectively inhibits the growth of MV4-11^Flt3-ITD, KG-1^{FGFR1OP2-FGFR1} and EOL-1^{FIP1L1-PDGFRa} cells, and also effectively suppresses the growth of Ba/F3-FLT3-ITD cells harboring F691I and other mutations with IC₅₀ values <10 nM. GZD824 induces G0/G1 phase arrest and apoptosi

SUBMITTER: Wang Y 

PROVIDER: S-EPMC7125355 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature