S81189
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- 公司名稱 上海源葉生物科技有限公司
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- 廠商性質(zhì) 生產(chǎn)廠家
- 更新時(shí)間 2024/7/2 20:18:53
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- 產(chǎn)品描述：
Onvansertib, also know as NMS-P937, PCM-075 and NMS1286937, is a n orally bioavailable, small-molecule Polo-like kinase 1 (PLK1) inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor 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. PLK1 inhibition may result in the inhibition of proliferation in PLK1-overexpressing tumor cells. PLK1 is a serine/threonine protein kinase crucial in the regulation of mitosis.
- 靶點(diǎn)： PLK1,；MELK,；CK2；FLT3
- 體外研究： NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with IC50 of 2 nM. NMS-1286937 also shows inhibitory activities against FLT3, MELK, and CK2, with IC50s of 510, 744, and 826 nM, respectively. NMS-P937 possesses a pure ATP competitive mechanism with a reversible dissociation and no time dependency. NMS-P937 (10 μM) is selective with a marginal activity of 48% and 40% inhibition on PLK2 and PLK3, respectively. NMS-P937 shows antiproliferative 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 μM for only 9 of 137 cell lines. NMS-P937 shows cytotoxic activity against AmL-NS8 cells with IC50 of 36 nM.
- 體內(nèi)研究： NMS-1286937 (45 mg/kg, i.v.) shows a good tumor growth inhibition with acceptable and reversible body weight 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. NMS-P937 (45 mg/kg, i.v.or 60 mg/kg, p.o) inhibits tumor growth to a comparable degree (TGI, 83% and 79% intravenously and orally, respectively) in HCT116-bearing mice. The combination of NMS-P937 (120 mg/kg given for 4 cycles of 2 consecutive days with 10-day rest) and cytarabine (75 mg/kg for 4 cycles of 5 consecutive days with 7-day rest) in the disseminated leukemia model AmL-PS is well tolerated and clearly showed increased mice survival. NMS-P937 (60 mg/kg bid os per day over 2 days with a 5 day rest) shows good efficacy compared to standard therapies, with a significant increase in median survival time (MST) in the established disease setting.
- 參考文獻(xiàn)：
1. Beria I, 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 May 15;21(10):2969-74.
2. Valsasina B, 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 Apr;11(4):1006-16.
3. Casolaro A, et al. The Polo-Like Kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia. PLoS One. 2013;8(3):e58424.
- 溶解度： DMSO: 21 mg/mL
- 保存條件： -20℃
- 配置溶液濃度參考：
1mg 5mg 10mg 1 mM 1.878 ml 9.389 ml 18.779 ml 5 mM 0.376 ml 1.878 ml 3.756 ml 10 mM 0.188 ml 0.939 ml 1.878 ml 50 mM 0.038 ml 0.188 ml 0.376 ml
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