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5mg |
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25mg |
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50mg |
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500mg |
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Purity: ≥98%
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 exhibits 5000-fold selectivity over PLK2/PLK3 and an IC50 of 2 nM for inhibiting PLK1. NMS-1286937 selectively inhibits PLK1, causing reversible cell-cycle arrest at the G1 and G2 stages without apoptosis in normal cells, and selective G2/M cell-cycle arrest followed by apoptosis in a variety of tumor cells. Following oral administration, NMS-P937 demonstrated activity in vivo in the HCT116 xenograft model. The drug is currently being evaluated in Phase I clinical trials.
Targets |
PLK1 (IC50 = 2 nM); FLT3 (IC50 = 510 nM); MELK (IC50 = 744 nM); CK2 (IC50 = 826 nM)
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ln Vitro |
NMS-P937 demonstrates broad-spectrum antiproliferative activity against cell lines from lymphomas, leukemias, and solid tumors. In A2780 cells, NMS-P937 potently induces a mitotic cell-cycle arrest that is followed by apoptosis.[2]
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ln Vivo |
NMS-P937 (90 mg/kg/d i.v. or p.o.) significantly inhibits the growth of tumors in mice xenografted with human HCT116 colon adenocarcinoma cells.[1]
NMS-P937 inhibits xenograft tumor growth in mice with HT29, Colo205 colorectal, or A2780 ovarian xenograft tumors. Furthermore, when used with authorized cytotoxic medications, NMS-P937 promotes improved tumor regression and increases animal survival.[2] |
Enzyme Assay |
Using a trans-phosphorylation assay, the potency of particular compounds and the inhibitory activity of putative kinase inhibitors are assessed. Under optimal buffer and cofactor conditions, a particular tyrosine kinase or serine-threonine kinase will trans-phosphorylate a specific peptide or protein substrate in the presence of ATP traced with 33P-γ-ATP. An excess of the ion exchange Dowex resin is added at the end of the phosphorylation reaction to capture over 98% of the unlabeled ATP and radioactive ATP; the resin then falls to the bottom of the reaction plate due to gravity. The phosphorylated substrate-containing supernatant is then extracted and put into a counting plate for analysis using b-counting. At 25 °C, an end-point assay lasting 60 minutes was used to assess the inhibitory potency of all the kinases that were tested. The substrate and ATP concentrations were maintained at 2 x αKm and >5 x αKm, respectively.
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Cell Assay |
In suitable medium supplemented with 10% fetal calf serum, cells are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 for adherent cells and 100,000/mL for nonadherent cells. Cells were treated in duplicate with NMS-P937 serial dilutions after a 24-hour period, and the CellTiter-Glo Assay (Promega) was used to determine the viable cell count 72 hours later. Using the Assay Explorer MDL sigmoidal fitting algorithm, IC50 values were determined. At least two independent experiments were conducted.
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Animal Protocol |
Female Hsd athymic nu/nu mice, aged 5 to 6 weeks (average weight: 20–22 g), are used for carcinoma xenograft studies. Subcutaneous inoculation is used to inoculate the colorectal HCT116, HT29, ovarian human carcinoma A2780, and colono205 cell lines. Treatment begins the day after randomization and involves giving vehicle or NMS-P937 to mice with a palpable tumor (100-200 mm3) according to prescribed doses and schedules. Tumor growth inhibition (TGI) is calculated and tumor dimensions are routinely measured using Vernier callipers. Reduction of body weight is used to assess toxicity. Severe combined immunodeficient mice (SCID; average weight: 20–22 g) that are 5–6 weeks old are used for leukemia research. Treatments begin with subcutaneous injections of the AmL cell line HL-60 (5×106 cells) and end when the tumor size reaches 200 to 250 mm3. TGI and tumor dimensions are evaluated. Treatments for disseminated models begin two days after intravenous injection of 5x106 AmL primary cells (AmL-PS). Every day, mice are checked for disease-related symptoms, and the median survival period for each group is calculated.
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References |
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Molecular Formula |
C24H27F3N8O3
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Molecular Weight |
532.52
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Exact Mass |
532.22
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Elemental Analysis |
C, 54.13; H, 5.11; F, 10.70; N, 21.04; O, 9.01
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CAS # |
1034616-18-6
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Appearance |
Solid powder
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SMILES |
CN1CCN(CC1)C2=CC(=C(C=C2)OC(F)(F)F)NC3=NC=C4CCC5=C(C4=N3)N(N=C5C(=O)N)CCO
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InChi Key |
QHLVBNKYJGBCQJ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C24H27F3N8O3/c1-33-6-8-34(9-7-33)15-3-5-18(38-24(25,26)27)17(12-15)30-23-29-13-14-2-4-16-20(22(28)37)32-35(10-11-36)21(16)19(14)31-23/h3,5,12-13,36H,2,4,6-11H2,1H3,(H2,28,37)(H,29,30,31)
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Chemical Name |
1-(2-hydroxyethyl)-8-[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)anilino]-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8779 mL | 9.3893 mL | 18.7786 mL | |
5 mM | 0.3756 mL | 1.8779 mL | 3.7557 mL | |
10 mM | 0.1878 mL | 0.9389 mL | 1.8779 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
PLK1 expression in AML-NS8 cells and activity of PLK1 inhibitor NMS-937in vitroandin vivo.PLoS One.2013;8(3):e58424. th> |
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Leukaemic infiltration of meninges and soft tissues from mice treated with NMS-P937 and cytarabine following a therapeutic schedule.PLoS One.2013;8(3):e58424. td> |
Mechanism of action of PLK1 inhibitorin vitroandin vivo.PLoS One.2013;8(3):e58424. td> |