MLN0905 (PLK1 Inhibitor) is an effective PLK1 inhibitor(IC50=2 nM).

PLK1:2 nM

In nude mice bearing HT-29 xenografts, oral administration of MLN0905 (6.25 mg / Kg-50 mg / Kg) demonstrated a dose-dependent pharmacological response 48 hours post-treatment. Similarly, in mice harboring OCI LY-19-Luc tumors, oral MLN0905 (3.12 mg / Kg-6.25 mg / Kg) showed a pharmacological response 8 hours after treatment.

MLN0905 acts as a potent inhibitor of PLK1, exhibiting an IC50 value of 2 nM. It effectively hampers cell mitosis with an EC50 of 9 nM and inhibits cell proliferation in HT-29 cells, as evidenced by an LD50 of 22 nM. Furthermore, in a range of lymphoma cell lines, MLN0905 demonstrates the ability to diminish cell viability, with IC50 values ranging from 3 to 24 nM.

PLK1 Flash Plate Assay: The human PLK1 enzymatic reaction totaling 30μL contained 50 mM Tris-HCl (pH 8.0), 10 mM MgCl2, 0.02% BSA, 10% glycerol, 1 mM DTT, 100 mM NaCl, 3.3% DMSO, 8 μM ATP, 0.2μCi [γ- 33 P]-ATP, 4 μM peptide substrate (Biotin-AHX-LDETGHLDSSGLQEVHLA-CONH2), and 10 nM recombinant human PLK1[2–369]T210D. The enzymatic reaction mixture, with or without PLK inhibitors, is incubated for 2.5 h at 30℃before termination with 20μL of 150 mM EDTA. Then 25μL of the stopped enzyme reaction mixture is transferred to a 384-well streptavidin coated Image FlashPlate and incubated at room temperature for 3 h. The Image Flash Plate wells are washed three times with 0.02% Tween-20 and then read on the Perkin-Elmer Viewlux.