PSTK inhibitor

PSTK inhibitors are a class of therapeutic compounds designed to target Phosphoseryl-tRNA kinase (PSTK), a specialized kinase essential for the biosynthesis of selenocysteine, the 21st amino acid. By inhibiting PSTK, these agents prevent the conversion of seryl-tRNA[Sec] to phosphoseryl-tRNA[Sec], thereby disrupting the production of all selenoproteins, including the key antioxidant enzyme Glutathione peroxidase 4 (GPX4). Research conducted by institutions such as Harvard University and Massachusetts General Hospital has demonstrated that PSTK inhibition induces a self-amplifying feedback loop involving mitochondrial reactive oxygen species (ROS) production, mitochondrial DNA release, and activation of the cGAS-STING innate immune signaling pathway. This cascade leads to ferroptotic cell death, particularly in leukemic stem cells (LSCs) within acute myeloid leukemia (AML) models. PSTK inhibitors, such as the naturally derived compound punicalin, have shown potential in sensitizing chemoresistant AML cells to therapy and clearing malignant populations while sparing normal hematopoietic cells.

Other names

PSTK inhibitorsPhosphoseryl-tRNA kinase inhibitorsPSTK inhibitor