瑞博西尼作用机制 - Medchemexpress - MCE中国

1、Product Data SheetRibociclibCat. No.: HY-15777CAS No.: 1211441-98-3分式: CHNO分量: 434.54作靶点: CDK作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 5.4 mg/mL (12.43 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.3013 m

2、L 11.5064 mL 23.0128 mL5 mM 0.4603 mL 2.3013 mL 4.6026 mL10 mM 0.2301 mL 1.1506 mL 2.3013 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。BIOLOGICAL ACTIVITY物活性 Ribociclib (LEE011)种度特异性的 CDK4/6 抑制剂，IC50 值分别为 10 nM 和

3、 39 nM，对 cyclin B/CDK1 复合体的活性低于其 1000 倍。IC & Target CDK4 CDK610 nM (IC50) 39 nM (IC50)体外研究Treating a panel of 17 neuroblastoma cell lines with Ribociclib (LEE011) across a four-log dose range (10 to 10,000nM). Treatment with Ribociclib significantly inhibits substrate adherent growth relative to the

4、 control in 12 of the 17neuroblastoma cell lines examined (mean IC50=30668 nM, considering sensitive lines only, where sensitivity isdefined as an IC50 of less than 1 M. Ribociclib treatment of two neuroblastoma cell lines (BE2C and IMR5) withdemonstrated sensitivity to CDK4/6 inhibition results in

5、a dose-dependent accumulation of cells in the G0/G1 phaseof the cell cycle. This G0/G1 arrest becomes significant at Ribociclib concentrations of 100 nM (p=0.007) and 250 nMPage 1 of 2 www.MedChemE(p=0.01), respectively2.体内研究 CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive

6、 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 dosing strategy is well tolerated, as no weight loss or other signs of toxicity are observed in any of thexenograft models. Tumor gr

7、owth is significantly delayed throughout the 21 days of treatment in mice harboring theBE2C or 1643 xenografts (both, p0.0001), although growth resumed post-treatment2.PROTOCOLCell Assay 2 Cells are grown for 24 hours in 35 mm plates, treated with 500 nM Ribociclib (LEE011) for 6 days, and then fixe

8、d andstained overnight. Cells are then imaged for SA-gal using an Axio Observer D.1 phase contrast microscope. Thepercentage of SA-gal positive cells is determined by counting the number of positive cells present in threeseparate microscope frames, and then normalizing to the control. To assess apop

9、totic activity, cells are plated intriplicate in 96 well plates, treated with Ribociclib (LEE011), and assayed for caspase 3/7 activation 16 hours aftertreatment with Caspase-Glo 3/7. Cells treated with SN-38 are used as a positive control2.MCE has not independently confirmed the accuracy of these m

10、ethods. 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-/- mice. Animals bearing engrafted tumors of 200-600 mm3 are then randomized to oral treatment with 200mg/kg Ribocicl

11、ib (LEE011) in 0.5 % methylcellulose (n=10) or vehicle (n=10) daily for a total of 21 days. Tumorburden is determined periodically throughout treatment according to the formula (/6)d2, where d represents themean tumor diameter obtained by caliper measurement.MCE has not independently confirmed the a

12、ccuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Mol Cell. 2017 Oct 19;68(2):336-349.e6. Nat Commun. 2019 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 val

13、idations 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(22):6173-82.McePdfHeightPage 2 of 3 www.MedChemECaution: Pr