| NMS-1286937PLK1 inhibitor, orally bioavailable |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.00%
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Chemical structure
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| Cas No. | 1034616-18-6 | SDF | Download SDF |
| Formula | C24H27F3N8O3 | M.Wt | 532.52 |
| Solubility | ≥13.3mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
NMS-1286937 (NMS-P937) is a potent and selective inhibitor of Polo-like kinase 1 (PLK1) with IC50 value of 2 nM [1].
PLK1 is a serine/threonine protein kinase and plays an important role in the cell cycle control machinery. PLK1 is involved in mitotic entry, bipolar mitotic spindle formation, centrosome duplication, transition from metaphase to anaphase, maintenance of genomic stability and cytokinesis [1].
NMS-1286937 is an orally bioavailable PLK1 inhibitor. In cell lines established from solid tumors, leukemias and lymphomas, NMS-P937 inhibited tumor cell proliferation. In A2780 cells, NMS-P937 caused a G2-M cell-cycle block. In the mitotic phase, NMS-P937 induced apoptotic death with misaligned chromosomes and an aberrant number of spindles poles [2]. In human osteosarcoma (OS) cell lines, NMS-P937 inhibited migration and clonogenic ability of cell lines. In ABCB1-overexpressing, Doxorubicin (DX)-resistant cell lines, combination of NMS-P937 and DX reverted DX-resistance by inhibiting ABCB1 transport activity [3].
In Harlan nu/nu mice, NMS-P937 exhibited a good pharmacokinetic profile with low clearance, high AUC and Cmax, and acceptable oral bioavailability. In mice xenografted with human HCT116 colon adenocarcinoma cells, NMS-P937 (45 mg/kg) inhibited tumor growth by 83% and reduced body weight by 16% [1].
References:[1]. Beria I, Bossi RT, Brasca MG, et al. NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor. Bioorg Med Chem Lett, 2011, 21(10): 2969-2974.[2]. Valsasina B, Beria I, Alli C, et al. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. Mol Cancer Ther, 2012, 11(4): 1006-1016. [3]. Sero V, Tavanti E, Vella S, et al. Targeting polo-like kinase 1 by NMS-P937 in osteosarcoma cell lines inhibits tumor cell growth and partially overcomes drug resistance. Invest New Drugs, 2014, 32(6): 1167-1180.
