AMG-925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with in vitro IC50 values of 2 nM and 3 nM, respectively. In acute myeloid leukemia (AML) cell lines MOLM13 and Mv4-11, AMG 925 inhibits cell growth (with Cellular IC50 values of 19nM and 18nM, respectively) through inhibiting P-FLT3 and P-STAT5 and inducing apoptosis. AMG 925 inhibited AML xenograft tumor growth by 96% to 99% without significant body weight loss. The antitumor activity of AMG 925 correlated with the inhibition of STAT5 and RB phosphorylation, the pharmacodynamic markers for inhibition of FLT3 and CDK4, respectively. In addition, it was also found to inhibit FLT3 mutants (e.g., D835Y) that are resistant to the current FLT3 inhibitors (e.g., AC220 (Axon 1696) and Sorafenib (Axon 1397)).

Keywords: AMG-925 | Supplier | FLT3/CDK4 dual inhibitor | AMG925 | AMG 925 | FLX-925 | FLX 925 | CT-AMG925 | CAS [1401033-86-0] | Cyclin dependent (CDK) | CDK | FLT3 | Inhibitor | Enzymes