PD 0332991 (Palbociclib) HCl
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
PD-0332991是一种选择性的和可口服的细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂,IC50值分别为11 nM和16 nM[1]。
PD-0332991是一种高特异性的CDK4/6抑制剂。在Rb阳性肿瘤细胞中,PD-0332991是一种有效的抗增殖剂,特异性地诱导G1期停滞。据报道,PD-0332991阻止人骨髓瘤异种移植物中肿瘤的生长,诱导原代骨髓细胞中G1期停滞[2]。
对PD-0332991在乳腺癌中的作用也进行了研究。PD-0332991引起ER阳性细胞系和10/16 个HER2扩增细胞系的生长抑制。100 nM的PD-0332991可以抑制三个更敏感细胞系中Rb的磷酸化,从而阻止细胞周期进程[2]。
参考文献:
[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.
- 1. Schwartz, Hannah, et al. "In vitro Methods to Better Evaluate Drug Responses in Cancer." UMass Chan Medical School. September 8, 2022.
- 2. Paula Carpintero-Fernández, Michela Borghesan, et al. "Genome wide CRISPR/Cas9 screen identifies the coagulation factor IX (F9) as a regulator of senescence." Cell Death Dis. 2022 Feb 19;13(2):163. PMID: 35184131
- 3. Anca Nastase, Amit Mandal, et al. "Integrated genomics point to immune vulnerabilities in pleural mesothelioma." Sci Rep. 2021 Sep 27;11(1):19138. PMID: 34580349
- 4. Minghui Liu, Liyuan Cui, et al. "PD-0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance." Thorac Cancer. 2021 Mar;12(6):924-931. PMID: 33534964
- 5. Anca Nastase, Amit Mandal, et al. "Multiple therapeutic pathways in malignant mesothelioma identified by genomic mapping." medRxiv. March 30, 2020.
- 6. Borghesan M, Fafián-Labora J, et al. "Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3." Cell Rep. 2019 Jun 25;27(13):3956-3971.e6. PMID: 31242426
- 7. 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
- 8. 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
- 9. 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
- 10. 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
- 11. 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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 483.99 |
Cas No. | 827022-32-2 |
Formula | C24H30ClN7O2 |
Synonyms | PD0332991; PD-0332991; PD 0332991 |
Solubility | ≥14.48 mg/mL in H2O; ≥2.42 mg/mL in DMSO; ≥2.79 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride |
SDF | Download SDF |
Canonical SMILES | O=C1N(C2=NC(NC3=NC=C(C=C3)N4CCNCC4)=NC=C2C(C)=C1C(C)=O)C5CCCC5.Cl |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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或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. |
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 |
质量控制和MSDS
- 批次: