SKLB-677, an FLT3 and Wnt/β-catenin signaling inhibitor, displays potent activity in models of FLT3-driven AML.

ABSTRACT: FLT3 has been identified as a valid target for the treatment of acute myeloid leukemia (AML), and some FLT3 inhibitors have shown very good efficacy in treating AML in clinical trials. Nevertheless, recent studies indicated that relapse and drug resistance are still difficult to avoid, and leukemia stem cells (LSCs) are considered one of the most important contributors. Here, we report the characterization of SKLB-677, a new FLT3 inhibitor developed by us recently. SKLB-677 exhibits low nanomolar potency in biochemical and cellular assays. It is efficacious in animal models at doses as low as 1mg/kg when administrated orally once daily. In particular, SKLB-677 but not first-generation and second-generation FLT3 inhibitors in clinical trials has the ability to inhibit Wnt/β-catenin signalin

SUBMITTER: Ma S 

PROVIDER: S-EPMC4620497 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature