CAS:1211441-98-3
Storage:Powder:-20℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:Light yellow to brown Solid
是一种具有活性的,高度特异性CDK4/6抑制剂。
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RibociclibCAS:1211441-98-3
Storage:Powder:-20℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:Light yellow to brown Solid
CAS | 1211441-98-3 |
Chinese Name | 瑞柏司可里布 |
English Name | Ribociclib |
Synonyms | LEE011 |
Molecular Formula | C23H30N8O |
Molecular Weight | 434.54 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | Light yellow to brown Solid |
Storage | Powder:-20℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC | EINECS 1592732-453-0 |
MDL | MFCD27976795 |
SMILES | O=C(N(C)C)C(N1C2CCCC2)=CC(C1=N3)=CN=C3NC(N=C4)=CC=C4N5CCNCC5 |
Target Point | CDK4,CDK6 |
Passage | Cell Cycle |
Background | Ribociclib is an active, highly specific CDK4/6 inhibitor. |
Biological Activity | Ribociclib (LEE011) 是高选择性的 CDK4/6 抑制剂, IC50 分别为10 nM, 39 nM[1-3]。 |
IC50 | CDK4:10nM (IC50) CDK6:39nM (IC50) [1-3] |
In Vitro | 用Ribociclib(LEE011)处理一组17个神经母细胞瘤细胞系,跨越4个对数剂量范围(10到10,000nM)。在检查的17种成神经细胞瘤细胞系中,12种神经母细胞瘤细胞系中使用Ribociclib治疗显着抑制底物贴壁生长(平均IC50 = 306±68 nM,仅考虑敏感细胞系,灵敏度定义为IC50小于1μM.Ribociclib治疗两种神经母细胞瘤细胞系(BE2C和IMR5)对CDK4 / 6抑制具有明显的敏感性,导致细胞周期G0 / G1期细胞的剂量依赖性积累。这种G0 / G1停滞在Ribociclib浓度为100时显着增加nM(p = 0.007)和250 nM(p = 0.01),分别为[2]。 |
In Vivo | 携带BE2C,NB-1643(MYCN扩增,体外敏感)或EBC1(非扩增,体外抗性)异种移植物的CB17免疫缺陷小鼠每日一次用Ribociclib(LEE011; 200mg / kg)或用车辆控制。该给药策略耐受性良好,因为在任何异种移植模型中均未观察到体重减轻或其他毒性迹象。在携带BE2C或1643异种移植物的小鼠中,肿瘤生长在整个21天内显着延迟(两者,p <0.0001),尽管在治疗后恢复生长[2]。 |
Cell Experiment | 细胞在35mm平板中生长24小时,用500nM Ribociclib(LEE011)处理6天,然后固定并染色过夜。然后使用Axio Observer D.1相差显微镜对细胞进行SA-β-gal成像。通过计数存在于三个单独的显微镜框架中的阳性细胞的数量,然后归一化至对照,确定SA-β-gal阳性细胞的百分比。为了评估细胞凋亡活性,将细胞一式三份接种在96孔板中,用Ribociclib(LEE011)处理,并在用Caspase-Glo 3/7处理后16小时测定胱天蛋白酶3/7活化。用SN-38处理的细胞用作阳性对照[2]。 |
Animal Experiment | 小鼠[2]将BE2C,NB-1643或EBC1细胞系衍生的异种移植物皮下植入CB17 SCID - / - 小鼠的右胁腹。然后将携带200-600mm 3的移植肿瘤的动物随机分配至每天用0.5mg甲基纤维素(n = 10)或载体(n = 10)中的200mg / kg Ribociclib(LEE011)口服治疗,总共21天。根据公式(π/ 6)×d2在整个治疗期间定期确定肿瘤负荷,其中d表示通过卡尺测量获得的平均肿瘤直径。 |
Data Literature Source | [1]. 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. [3]. Olanich ME, et al. CDK4 Amplification Reduces Sensitivity to CDK4/6 Inhibition in Fusion-Positive Rhabdomyosarcoma. Clin Cancer Res. 2015 Nov 1; 21 (21) :4947-59. |
Unit | Bottle |
Specification | 5mg 10mg 20mg |
是一种具有活性的,高度特异性CDK4/6抑制剂。