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Description: MLN0905 (MLN-0905; MLN 0905) is a novel, potent and selective small-molecule inhibitor of polo-like kinase-1 (PLK1) with potential antineoplastic activity. It inhibits PLK1 with an IC50 of 2 nM. MLN0905 inhibits cell proliferation in a broad range of human tumor cells including DLBCL cell lines. PLK1 inhibition leads to pharmacodynamic pHisH3 modulation and significant antitumor activity in multiple DLBCL models. These data strongly suggest evaluating PLK1 inhibitors as DLBCL anticancer agents in the clinic.
References: J Med Chem. 2012 Jan 12;55(1):197-208; Mol Cancer Ther. 2012 Sep;11(9):2045-53.
Product Catalog 2022
Guide to Product Handling
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: MLN0905 is a potent inhibitor of PLK1 with IC50 of 2 nM. MLN0905 inhibits cell mitosis with EC50 of 9 nM. MLN0905 inhibits Cdc25C-T96 phosphorylation, a direct readout of PLK1 inhibition with EC50 of 29 nM. MLN0905 inhibits HT-29 viability with LD50 of 22 nM. MLN0905 possesses reasonable selectivity against a panel of 359 kinases. MLN0905 inhibits a panel of lymphoma cells viability with IC50 of 3 – 24 nM.
Kinase 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, 4μM 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.
Cell Assay: MLN0905 is a selective PLK1 inhibitor and has similar effect as RNAi hnockdown. When tested with HT-29 cells, MLN0905 treatment significantly increased pHisH3 expression which indicated that cells were arrested in G2/M phase by inhibiting PLK1 expression.
Purity ≥98%
COA
MSDS
MLN0905 induces a significant antitumor response in mice bearing disseminated (human) OCI LY-19-Luc lymphoma disease.
pHisH3 was used as a biomarker to determine the level of mitotic arrest in OCI LY-19-Luc xenograft tumors. Mol Cancer Ther. 2012 Sep;11(9):2045-53.
MLN0905, a small-molecule inhibitor of PLK1, phenocopies the effects of PLK1 knockdown using RNAi in HT-29 cells.
MLN0905 induces a significant antitumor response in a primary human lymphoma model (PHTX-22L). Mol Cancer Ther. 2012 Sep;11(9):2045-53.
MLN0905 and rituximab yield a synergistic antitumor response in a disseminated xenograft model of human lymphoma (OCI LY-19-Luc).
Evaluating the effect of dosing schedule versus antitumor effect with MLN0905 in the OCI LY-10 subcutaneous tumor model. Mol Cancer Ther. 2012 Sep;11(9):2045-53.