| References: |
PIM447 is novel pan-PIM kinase inhibitor, including Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase.
In vitro: PIM447 is cytotoxic for myeloma cells due to cell cycle disruption and induction of apoptosis mediated by a decrease in phospho-Bad (Ser112) and c-Myc levels and the inhibition of mTORC1 pathway. PIM447 also inhibits in vitro osteoclast formation and resorption, downregulates key molecules involved in these processes and partially disrupts the F-actin ring, while increasing osteoblast activity and mineralization.
In vivo: PIM447 significantly reduces the tumor burden and preventes tumor-associated bone loss in a disseminated murine model of human myeloma. |
