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Palbociclib isethionate

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Chemical Structure| 827022-33-3 同义名 : 帕布昔利布羟乙基磺酸盐 ;PD 0332991 isethionate
CAS号 : 827022-33-3
货号 : A280869
分子式 : C26H35N7O6S
纯度 : 99%+
分子量 : 573.664
MDL号 : MFCD22666589
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(15.69 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

H2O: 50 mg/mL(87.16 mM)，配合低频超声助溶
动物实验配方：

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • CDK4

    CDK4/CyclinD3, IC50:9 nM

    CDK4/CyclinD1, IC50:11 nM

  • CDK6

    CDK6/CyclinD2, IC50:15 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]. Palbociclib (PD 0332991) is a highly specific pyridopyrimidine-derived inhibitor of both CDK4 and CDK6 with IC50 values of 11 nM and 16 nM (measured by enzymatic activity), respectively. Treatment with 0.031 - 1 μM of palbociclib for 24h can decrease the level of Rb phosphorylation at Ser-780 in MDA-MB-435 human breast carcinoma cells. Palbociclib can potently inhibit cell growth in Rb-positive cells, such as MDA-MB-435, ZR-75-1, T-47D, MCF-7, H1299, Colo-205, CRRF-CEM and K562 cell lines, with IC50 values of 0.04 - 0.4 μM, as well as suppress DNA replication by preventing cells from entering S phase. Daily p.o. dosing for 14 days with palbociclib (150 or 75 mg/kg) can produce rapid tumor regressions in p16 deleted mice bearing Colo-205 colon carcinoma xenografts[2]. Up to now, several phase 3 studies on Palbociclib of treatment for breast cancer are undergoing (see on https://www.clinicaltrials.gov/).
作用机制 Palbociclib can inhibit CDK4/6 in an ATP-competitive manner through its pyridopyrimidine structure.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
H157 0-100 μM Growth Inhibition Assay 72 h IC50=9 μM 26390342
H2170 0-100 μM Growth Inhibition Assay 72 h IC50=5 μM 26390342
H520 0-100 μM Growth Inhibition Assay 72 h IC50=0.73 μM 26390342
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.74mL

0.35mL

0.17mL

8.72mL

1.74mL

0.87mL

17.43mL

3.49mL

1.74mL
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]Fry DW, Harvey PJ, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.

[3]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.

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