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    NMS-P937 (NMS1286937; Onvansertib)
    NMS-P937 (NMS1286937; Onvansertib)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1580
    CAS #: 1034616-18-6Purity ≥98%

    Description: NMS-P937 (also know as NMS-P937; NMS1286937; NMS-P-937; NMS-P 937; Onvansertib) is an orally bioavailable, potent, selective, small-molecule Polo-like Kinase 1 (PLK1) inhibitor with potential antitumor activity. It inhibits PLK1 with an IC50 of 2 nM and 5000-fold selectivity over PLK2/PLK3. NMS-1286937 selectively inhibits PLK1, inducing selective G2/M cell-cycle arrest followed by apoptosis in a variety of tumor cells while causing reversible cell-cycle arrest at the G1 and G2 stages without apoptosis in normal cells. NMS-P937 was active in vivo in HCT116 xenograft model after oral administration and is presently in Phase I clinical trials evaluation.

    References: Bioorg Med Chem Lett. 2011 May 15;21(10):2969-74; Mol Cancer Ther. 2012 Apr;11(4):1006-16.

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    Molecular Weight (MW)532.52
    CAS No.1034616-18-6
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 42 mg/mL (78.9 mM)
    Water:<1 mg/mL
    Ethanol: 10 mg/mL (18.8 mM)
    Synonyms NMS-P937; NMS1286937; NMS-P-937; NMS-P 937; NMS 1286937; NMS-1286937

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    In Vitro

    In vitro activity: NMS-P937 shows a broad-spectrum antiproliferative activity against different solid tumor, leukemias and lymphomas cell lines. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in A2780 cells.

    Kinase Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds are determined using a trans-phosphorylation assay. Specific peptide or protein substrates are trans-phosphorylated by their specific serine-threonine or tyrosine kinase, in the presence of ATP traced with 33P-γ-ATP, at optimized buffer and cofactors conditions. At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP is captured by adding an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity. Supernatant, containing the phosphorylated substrate, is subsequently withdrawn and transferred into a counting plate, followed by evaluation by b-counting. Inhibitory potency evaluation for all the tested kinases was performed at 25 °C using a 60 min end-point assay where the concentrations of ATP and substrates are kept equal to 2 x αKm and saturated (>5 x αKm), respectively.

    Cell Assay: Cells (137 solid tumor cell lines, and 43 cell lines derived from leukemias and lymphomas) are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 for adherent and 100,000/mL for nonadherent cells in appropriate medium supplemented with 10% fetal calf serum. After 24 hours, cells were treated in duplicate with serial dilutions of NMS-P937, and 72 hours later, the viable cell number was assessed by the CellTiter-Glo Assay (Promega). IC50 values were calculated with a sigmoidal fitting algorithm (Assay Explorer MDL). Experiments were carried out independently at least twice.

    In VivoIn mice xenografted with human HCT116 colon adenocarcinoma cells, NMS-P937 (90 mg/kg/d i.v. or p.o.) shows a significant tumor growth inhibition. In mice bearing HT29, Colo205 colorectal, or A2780 ovarian xenograft tumors, NMS-P937 inhibits xenograft tumor growth. In addition, NMS-P937, in combination with approved cytotoxic drugs, causes enhanced tumor regression, and prolongs survival of animals.
    Animal model Mice xenografted with human HCT116 colon adenocarcinoma cells
    Formulation & Dosage 90 mg/kg/d i.v. or p.o.
    ReferencesBioorg Med Chem Lett. 2011 May 15;21(10):2969-74; Mol Cancer Ther. 2012 Apr;11(4):1006-16.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    NMS-P937 (NMS1286937)

    PLK1 expression in AML-NS8 cells and activity of PLK1 inhibitor NMS-937 in vitro and in vivo.  2013;8(3):e58424.


    NMS-P937 (NMS1286937)

    Leukaemic infiltration of meninges and soft tissues from mice treated with NMS-P937 and cytarabine following a therapeutic schedule.  2013;8(3):e58424.


    NMS-P937 (NMS1286937)

    Mechanism of action of PLK1 inhibitor in vitro and in vivo.  2013;8(3):e58424.


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