HDAC I/IIb selective inhibitor Purinostat Mesylate combined with GLS1 inhibition effectively eliminates CML stem cells.

ABSTRACT: Purinostat Mesylate (PM) is a novel highly selective and active HDAC I/IIb inhibitor, and the injectable formulation of PM (PMF) based on the compound prescription containing cyclodextrin completely can overcome PM's poor solubility and improves its stability and pharmacokinetic properties. Here, we showed that PM effectively repressed the survival of Ph⁺ leukemia cells and CD34⁺ leukemia cells from CML patients in vitro. In vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I) induced CML progression by restraining leukemia stem cells (LSCs), which are insensitive to chemotherapy and responsible for CML relapse. Mechanism studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc,

SUBMITTER: Qiu Q 

PROVIDER: S-EPMC9486186 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature