A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.

ABSTRACT: Acute leukemia is a highly heterogeneous disease; therefore, combination therapy is commonly used for patient treatment. Drug-drug interaction is a major concern of combined therapy; hence, dual/multi-target inhibitors have become a dominant approach for cancer drug development. HDACs and HSP90 are involved in the activation of various oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, and RAF/MEK/ERK, which are also highly enriched in acute leukemia gene expression profiles. Therefore, we suggest that dual HDAC and HSP90 inhibitors could represent a novel therapeutic approach for acute leukemia. MPT0G449 is a dual effect inhibitor, and it showed cytotoxic effectiveness in acute leukemia cells. Molecular docking analysis indicated that MPT0G449 possessed dual HDAC and HSP90 i

SUBMITTER: Wu YW 

PROVIDER: S-EPMC8119482 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature