NMS-1286937-NMS-P937-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENMS-1286937Cat. No.: HY-15828CAS No.: 1034616-18-6Synonyms: NMS-P937分式: CHFNO分量: 532.52作靶點(diǎn): Polo-like Kinase (PLK)作通路: Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 2

2、1 mg/mL (39.44 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.8779 mL 9.3893 mL 18.7786 mL5 mM 0.3756 mL 1.8779 mL 3.7557 mL10 mM 0.1878 mL 0.9389 mL 1.8779 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 nMS-1286937種有效、選擇性、可服的 PLK1 抑制劑，IC50

3、 值為 2 nM。IC50 & Target PLK1 MELK CK2 FLT32 nM (IC50) 744 nM (IC50) 826 nM (IC50) 510 nM (IC50)體外研究NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with IC50 of 2 nM. NMS-12869371/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEalso shows inhibitory activities against FLT3, MELK

4、, and CK2, with IC50s of 510, 744, and 826 nM,respectively 1. NMS-P937 possesses a pure ATP competitive mechanism with a reversible dissociation andno time dependency. NMS-P937 (10 M) is selective with a marginal activity of 48% and 40% inhibition onPLK2 and PLK3, respectively. NMS-P937 shows antipr

5、oliferative activity against a panel of 137 cell lines,with IC50 values of below 100 nM for 60 of 137 cell lines and higher than 1 M for only 9 of 137 cell lines 2.NMS-P937 shows cytotoxic activity against AmL-NS8 cells with IC50 of 36 nM 3.體內(nèi)研究 NMS-1286937 (45 mg/kg, i.v.) shows a good tumor growth

6、 inhibition with acceptable and reversible bodyweight loss in CD1 nu/nu mice xenografted with human HCT116 colon adenocarcinoma cells. NMS-1286937(60 mg/kg, p.o.) also inhibits the growth of tumor on HCT116 xenograft model 1. NMS-P937 (45 mg/kg,i.v.or 60 mg/kg, p.o) inhibits tumor growth to a compar

7、able degree (TGI, 83% and 79% intravenously andorally, respectively) in HCT116-bearing mice. The combination of NMS-P937 (120 mg/kg given for 4 cycles of2 consecutive days with 10-day rest) and cytarabine (75 mg/kg for 4 cycles of 5 consecutive days with 7-dayrest) in the disseminated leukemia model

8、 AmL-PS is well tolerated and clearly showed increased micesurvival 2. NMS-P937 (60 mg/kg bid os per day over 2 days with a 5 day rest) shows good efficacycompared to standard therapies, with a significant increase in median survival time (MST) in the establisheddisease setting 3.PROTOCOLKinase Assa

9、y 1 The inhibitory activity of putative kinase inhibitors and the potency of selected compounds are determinedusing a trans-phosphorylation assay. Specific peptide or protein substrates are trans-phosphorylated by theirspecific serine-threonine or tyrosine kinase, in the presence of ATP traced with

10、33P-ATP, at optimizedbuffer and cofactors conditions. At the end of the phosphorylation reaction, more than 98% unlabeled ATPand radioactive ATP is captured by adding an excess of the ion exchange dowex resin; the resin then settlesdown to the bottom of the reaction plate by gravity. Supernatant, co

11、ntaining the phosphorylated substrate, issubsequently withdrawn and transferred into a counting plate, followed by evaluation by b-counting. Inhibitorypotency evaluation for all the tested kinases is performed at 25C using a 60 min end-point assay where theconcentrations of ATP and substrates are ke

12、pt equal to 2 Km and saturated (5 Km), respectively.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Cells are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 for adherent and100,000/mL for nonadherent cells

13、 in appropriate medium supplemented with 10% fetal calf serum. After 24hours, cells are treated in duplicate with serial dilutions of NMS-P937, and 72 hours later, the viable cellnumber is assessed by the CellTiter-Glo Assay. IC50 values are calculated with a sigmoidal fitting algorithm.Experiments

14、are carried out independently at least twice.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal For carcinoma xenograft studies, 5- to 6-week-old female Hsd, athymic nu/nu mice (average weight, 20-22Administration 2 g), are used. HCT116, HT29, Colo2

15、05 colorectal, and A2780 ovarian human carcinoma cell lines areinoculated subcutaneously. Mice bearing a palpable tumor (100-200 mm3) are treated with vehicle or NMS-P937 following doses and schedules starting from the day after randomization. Tumor dimensions aremeasured regularly with Vernier cali

16、pers, and tumor growth inhibition (TGI) is calculated. Toxicity is2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEevaluated on the basis of body weight reduction. For leukemia studies, 5- to 6-week-old female severecombined immunodeficient mice (SCID; average weight, 20-22 g) are used. The AmL cell

17、 line HL-60 (5106cells) is injected subcutaneously and treatments initiated when tumor size reaches 200 to 250 mm3. Tumordimensions and TGI are assessed. For disseminated models, 5106 AmL primary cells (AmL-PS) areinjected intravenously and treatments start after 2 days. Mice are monitored daily for

18、 clinical signs of disease,and the median survival time is determined for each group.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Science. 2017 Dec 1;358(6367). Comput Struct Biotechnol J. 2019 Feb 8;17:352-361. Sci Rep. 2017 Aug 17;7(1):8629. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Beria I, et al. NMS-P937, a 4,5-dihydro-1H-pyrazolo4,3-hquinazoline derivative as potent and selective Polo-like kinase 1 inhibitor.Bioorg Med Chem Lett. 201