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Ribociclib

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Chemical Structure| 1211441-98-3 同义名 : 瑞博西利 ;LEE011
CAS号 : 1211441-98-3
货号 : A288696
分子式 : C23H30N8O
纯度 : 98%
分子量 : 434.537
MDL号 : -
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 5 mg/mL(11.51 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 5% DMSO+water 0.5 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • CDK4

    CDK4, IC50:10 nM

  • CDK6

    CDK6, IC50:39 nM
描述 CDK4/6, forming a complex with its partner Cyclin D1/2/3, can mediate the phosphorylation of Rb in G1 cell cycle, as well as stimulating the synthesis cyclin E and D-type cyclins controlled by extracellular mitogens[1]. LEE011 (Ribociclib) is an orally bioavailable dual CDK4/6 inhibitor with IC50 values of 10 nM and 40 nM, respectively[2]. Treatment of LEE011 (0.25 - 10 μM) can cause decrease in pRB-S780 accompany growth suppression in BE2C, EBC1, IMR5 and SKNAS neuroblastoma cell lines by a dose-dependent manner. 100 - 250nM of LEE011 can cause accumulation of G0/G1 phase of the cell cycle and cellular senescence with decreased FOXM1 in BE2C and IMR5 cells. Treatment of once daily for 21 days with 200mg/kg LEE011 can suppress neuroblastoma growth in mice with subcutaneously implanted BE2C or 1643 xenografts[3]. There are currently 16 active clinical trials with LEE011 as single agent or in combination with other drugs of treatment for melanoma, breast cancer, neuroblastoma, malignant rhabdoid and lymphomas[4].
作用机制 LEE011 can inhibit CDK4/6 in an ATP-competitive manner through its pyrrolo[2,3d]pyrimidine core[5].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
1643 Growth Inhibition Assay 24 h IC50=147 nM 24045179
449 Growth Inhibition Assay 72 h inhibits cell growth dose dependently 25028469
449 3.33 μM Growth Inhibition Assay 24 h decreases the proportion of cells in S phase 25028469
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.30mL

0.46mL

0.23mL

11.51mL

2.30mL

1.15mL

23.01mL

4.60mL

2.30mL
参考文献

[1]Roskoski R Jr, et al. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacol Res. 2016 May;107:249-275.

[2]Finn RS, Aleshin A, et al. Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. Breast Cancer Res. 2016 Feb 9;18(1):17.

[3]Rader J, Russell MR, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.

[4]Aleem E, Arceci RJ, et al. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol. 2015 Apr 9;3:16.

[5]Barvian M, Boschelli DH, et al. Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.

[6]In vivo studies of LEE011

[7]209092orig1s000multidiscipliner