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PD 0332991 (Palbociclib) HCl

现货
Catalog No.
A8316
CDK4/6抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 500.00
现货
25mg
¥ 900.00
现货

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Background

PD-0332991 is selective and oral inhibitor of cyclin-dependent kinase 4/6 with IC50 values of 11nM and 16nM, respectively for CDK4 and CDK6 [1].

PD-0332991 is a highly specific inhibitor of CDK4/6. It is a potent anti-proliferative agent against Rb-positive tumor cells in vitro, subsequently inducing an exclusive G1 arrest. It has been reported to prevent tumor growth in disseminated human myeloma xenografts and induce G1 arrest in primary bone marrow cells [2].

PD-0332991 is also studied in breast cancer. It causes growth inhibition of ER-positive cell lines and 10/16 HER2-amplified cell lines. 100nM PD-0332991 can inhibit the phosphorylation of Rb in three more sensitive cell lines, resulting in prevention of cell cycle progression [2].

References:
[1] Ivan Diaz-Padilla, Lillian L. Siu and Ignacio Duran. Cyclin-dependent kinase inhibitors as potential targeted anticancer agents. Invest New Drugs. 2009, 27: 586–594.
[2] Richard S Finn, Judy Dering, Dylan Conklin, Ondrej Kalous, David J Cohen, Amrita J Desai, Charles Ginther, Mohammad Atefi, Isan Chen, Camilla Fowst, Gerret Los and Dennis J Slamon. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Research. 2009, 11: R77.

文献引用

1. Gasset-Rosa F, Lu S, et al. "Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death." Neuron.2019 Apr 17;102(2):339-357.e7. PMID:30853299
2. Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID:30038713
3. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID:29507054
4. Yuan J, Jiang YY, et al. "Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma." Cancer Res. 2017 Dec 1;77(23):6614-6626. PMID:28951465
5. Ma Y, Walsh MJ, et al. "CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors." Cell Host Microbe.2017 May 10;21(5):580-591.e7. PMID:28494239

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt483.99
Cas No.827022-32-2
FormulaC24H30ClN7O2
SynonymsPD0332991;PD-0332991;PD 0332991
Solubility≥2.4mg/mL in DMSO, ≥24.2mg/mL in H2O, ≥2.79 mg/mL in EtOH with ultrasonic and warming
Chemical Name6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride
SDFDownload SDF
Canonical SMILESO=C1N(C2=NC(NC3=NC=C(C=C3)N4CCNCC4)=NC=C2C(C)=C1C(C)=O)C5CCCC5.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

MDA-MB-453细胞

制备方法

该化合物在DMSO中的溶解度小于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

80 nM,24 hours

实验结果

不同浓度的PD 0332991处理MDA-MB-453乳腺癌细胞24小时,0.04 μmol/L PD 0332991处理使G1期细胞百分比显著增加,伴随着处于其它相细胞周期的细胞数目减少。在0.08 μmol/L时达到最大效应,即使在高达10 μmol/L的浓度下仍保持唯一的G1阻滞,这与对细胞周期完全不存在任何其它影响一致。

动物实验: [1]

动物模型

携带Colo-205结肠癌异种移植物的小鼠

给药剂量

口服,150 or 75 mg/kg,每天,持续14天

实验结果

PD 0332991引起快速的肿瘤消退,将相应的肿瘤生长延迟约50天,在测试的最高剂量下肿瘤细胞杀伤力大于 1 log。在37.5 mg/kg治疗期间,肿瘤缓慢消退。在低至12.5 mg/kg的剂量下,肿瘤生长延迟13天,意味着抑制90%的肿瘤生长速率。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Fry D W, Harvey P J, Keller P R, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Molecular cancer therapeutics, 2004, 3(11): 1427-1438.

生物活性

描述 Palbociclib (PD-0332991) HCl是CDK4/6的抑制剂,IC50值为11 nM/16 nM。
靶点 CDK4/cyclin D1 CDK6/cyclin D2        
IC50 11 nM 16 nM        

质量控制

化学结构

PD 0332991 (Palbociclib) HCl

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