POLRMT-IN-2 is a potent inhibitor of POLRMT, exhibiting significant antiproliferative activity in MOLM-13 cells with an IC50 of 1.01 μM. It disrupts mitochondrial function and induces apoptosis, making it a valuable candidate for research in acute myeloid leukemia (AML).

POLRMT-IN-2 (Compound 10a) exerts a dose-dependent inhibition on POLRMT activity in MOLM-13 cells over 48 hours, showing an EC50 value of 2.208 μM for ND1 expression suppression. The compound exhibits IC50 values of 1.01 μM for MOLM-13 cells, 3.24 μM for MV4-11 cells, and 14.17 μM for HL-60 cells after 48 hours of treatment. At 5 μM concentration for 48 hours, POLRMT-IN-2 reduces MOLM-13 cell proliferation, indicated by a decrease in EdU-positive cells and reduced Ki67 expression. At concentrations between 0 and 10 μM over 48 hours, POLRMT-IN-2 compromises mitochondrial function in MOLM-13 cells, evidenced by increased ROS levels, decreased ATP content, and lowered mitochondrial membrane potential, all in a concentration-dependent manner. Additionally, POLRMT-IN-2 induces apoptosis in MOLM-13 cells and decreases both the level and phosphorylation at site 473 of AKT.