The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and aurora kinases.

Despite the development of several Fms-like tyrosine kinase 3 () inhibitors that have improved outcomes in patients with -mutant acute myeloid leukemia (AML), drug resistance is frequently observed, which may be associated with the activation of additional pro-survival pathways, such as those regulated by BTK, aurora kinases (AuroK), and potentially others, in addition to acquired tyrosine kinase domain (TKD) mutations of gene. may not always be a driver mutation. We evaluated the anti-leukemia efficacy of the novel multi-kinase inhibitor CG-806, which targets FLT3 and other kinases, to circumvent drug resistance and target wild-type (WT) cells. The anti-leukemia activity of CG-806 was investigated by measuring apoptosis induction and analyzing the cell cycle using flow cytometry . CG-806 demonstrated superior anti-leukemia efficacy compared to commercially available FLT3 inhibitors, both and , regardless of mutational status. The mechanism of action of CG-806 may involve its broad inhibitory profile against FLT3, BTK, and AuroK. In mutant cells, CG-806 induced G1 phase blockage, whereas in WT cells, it resulted in G2/M phase arrest. Targeting FLT3 and Bcl-2 and/or Mcl-1 simultaneously results in a synergistic pro-apoptotic effect in mutant leukemia cells. The results of this study suggest that CG-806 is a promising multi-kinase inhibitor with anti-leukemic efficacy regardless of mutational status. A phase 1 clinical trial of CG-806 for the treatment of AML has been initiated (NCT04477291).