瑞博西尼鹽酸鹽作用機制 - Medchemexpress - MCE中國

1、Product Data SheetRibociclib hydrochlorideCat. No.: HY-15777ACAS No.: 1211443-80-9分式: CHClNO分量: 471作靶點: CDK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)體外實驗 H2O : 10 mg/mL (21.23 mM; Need ultrasonic)DMSO : 7.69 mg/mL (16.33 mM; Need ultrasonic)

2、SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.1231 mL 10.6157 mL 21.2314 mL5 mM 0.4246 mL 2.1231 mL 4.2463 mL10 mM 0.2123 mL 1.0616 mL 2.1231 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；旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適

3、當?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.77 mg/mL (1.63 mM); Clear solution此案可獲得 0.77 mg/mL (1.63 mM，飽和度未知) 的澄清溶液。以

4、 1 mL 作液為例，取 100 L 7.7 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.77 mg/mL (1.63 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 0.77 mg/mL (1.63 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 7.7 mg/mL

5、 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。BIOLOGICAL ACTIVITY物活性 Ribociclib hydrochloride (LEE011 hydrochloride) 種度特異性的 CDK4/6 抑制劑，IC50 值分別為 10 nM 和 39 nM ，對 cyclin B/CDK1 復合體的活性低于其 1000 倍。IC & Target CDK4 CDK610 nM (IC50) 39 nM (IC50)體外研究 Treating a panel of 17 neuroblastoma cell lines with Ribo

6、ciclib (LEE011) across a four-log dose range (10 to 10,000nM). Treatment with Ribociclib significantly inhibits substrate adherent growth relative to the control in 12 of the 17neuroblastoma cell lines examined (mean IC50=30668 nM, considering sensitive lines only, where sensitivity isdefined as an

7、IC50 of less than 1 M. Ribociclib treatment of two neuroblastoma cell lines (BE2C and IMR5) withdemonstrated sensitivity to CDK4/6 inhibition results in a dose-dependent accumulation of cells in the G0/G1 phaseof the cell cycle. This G0/G1 arrest becomes significant at Ribociclib concentrations of 1

8、00 nM (p=0.007) and 250 nM(p=0.01), respectively2.體內(nèi)研究 CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified,resistant in vitro) xenografts are treated once daily for 21 days with Ribociclib (LEE011; 200 mg/kg) or with a vehiclecontrol. This dos

9、ing strategy is well tolerated, as no weight loss or other signs of toxicity are observed in any of thexenograft models. Tumor growth is significantly delayed throughout the 21 days of treatment in mice harboring theBE2C or 1643 xenografts (both, p0.0001), although growth resumed post-treatment2.PRO

10、TOCOLCell Assay 2 Cells are grown for 24 hours in 35 mm plates, treated with 500 nM Ribociclib for 6 days, and then fixed and stainedovernight. Cells are then imaged for SA-gal using an Axio Observer D.1 phase contrast microscope. The percentageof SA-gal positive cells is determined by counting the

11、number of positive cells present in three separatemicroscope frames, and then normalizing to the control. To assess apoptotic activity, cells are plated in triplicate in96 well plates, treated with Ribociclib, and assayed for caspase 3/7 activation 16 hours after treatment with Caspase-Glo 3/7. Cell

12、s treated with SN-38 are used as a positive control2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice2Administration 2 The BE2C, NB-1643, or EBC1 cell line-derived xenografts are implanted subcutaneously into the right flank of CB17SCID-/- mi

13、ce. Animals bearing engrafted tumors of 200-600 mm3 are then randomized to oral treatment with 200mg/kg Ribociclib in 0.5 % methylcellulose (n=10) or vehicle (n=10) daily for a total of 21 days. Tumor burden isdetermined periodically throughout treatment according to the formula (/6)d2, where d repr

14、esents the meantumor diameter obtained by caliper measurement.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Page 2 of 3 www.MedChemE Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Mol Cell. 2017 Oct 19;68(2):336-349.e6. Nat Commun. 201

15、9 Jun 28;10(1):2860. Clin Cancer Res. 2015 Nov 1;21(21):4947-59. Cancer Res. 2019 Oct 15;79(20):5245-5259.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. VanArsdale T, et al. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res. 2015 Jul 1;21(13):2905-10.2. Rader J, et al. Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(