生物活性
Palbociclib (PD-0332991)是一种高度选择性的CDK4/6抑制剂，IC50为11 nM/16 nM，对CDK1/2/5， EGFR， FGFR， PDGFR， InsR等没有抑制活性。PD 0332991对CDK4/6具有绝对选择性，对其他CDKs几乎没有抑制活性。PD 0332991作用于MDA-MB-435乳腺癌细胞，有效降低Rb在Ser780 和 Ser795位点磷酸化，IC50分别为66 nM和63 nM。PD 0332991通过抑制细胞进入S期，有效抑制细胞生长，抑制 DNA复制。PD 0332991抑制胸苷渗透进Rb阳性人类乳腺癌(如MDA-MB-435, MCF-7), 结肠癌 (H1299), 和肺癌(Colo-205) 及白血病(CRRF-CEM和K562)的DNA中，IC50值为0.04-0.17 μM。PD 0332991显著增强MDA-MB-453在G1期的百分比。PD 0332991作用于CD138+原发性骨髓瘤细胞，初级非转化的B细胞，MM1.S和CAG HMCLs细胞系，抑制Rb磷酸化，IC50分别为 <0.1 μM, 0.05 μM, 和 60-70 nM。PD 0332991作用于CD138+原发性骨髓瘤细胞和初级非转化的B细胞，诱导细胞停滞在G1期。
化学数据
| 分子量 | 483.99 |
| 分子式 | C24H29N7O2.HCl |
| CAS号 | 827022-32-2 |
| 纯度 | 99.90% |
| 溶解性（25°C） | DMSO 4 mg/mL warmed
Water 30 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | HCT116, SW480, Lovo and LS174T cells |
| 方法 | Cell proliferation and colony formation assays
Cells were seeded in a 96-well plate at 2000–6000 cells/well, incubated overnight at 37°C to allow adhesion, and then treated with inhibitors for 72 hours. Cell proliferation was determined using MTS solution (Promega), and formal assessment for synergy performed per the Chou Talalay method [64, 65] using CompuSyn (ComboSyn, Inc, Paramus, NJ). For colony formation assay, cells were seeded in a 6-well plate at 8000– 80,000 cells/well, incubated overnight at 37°C to allow adhesion, and then treated with inhibitors for 2–3 weeks. Cell colonies were fixed with ice-cold methanol and stained with 1% crystal violet. The density of colonies over the plate area was quantified by ImageJ (NIH) [66]. For detection of exposed phosphatidylserine residues reflective of apoptosis, Annexin V-FITC apoptosis assay kit (BD Biosciences) was used. Cells were seeded at 500,000 cells/ well in 6-well plates, incubated overnight at 37°C to allow adhesion, and then treated with inhibitors for 72 hours. Cells were washed and stained with annexin V-FITC and propidium iodide, and flow cytometry was performed using the Gallios flow cytometer (Beckman Coulter) and analyzed with Kaluza flow analysis software (Beckman Coulter). To measure cell senescence, treated cells were stained for senescence-associated beta-galactosidase (Chemicon). Cells were seeded at 500,000 cells/well in 6-well plates, incubated overnight at 37°C to allow adhesion, and then treated with inhibitors for 72 hours. Cells were washed with PBS, fixed with glutaraldehyde and methanol, washed twice more, and then incubated overnight in the dark at 37°C under ambient atmospheric conditions with X-Gal. Subsequently, cells were washed, and 10 high-powered light microscopy images of each well were captured, and cells with blue staining were manually counted. |
| 浓度 | 0~400nM |
| 处理时间 | 72 h |
| 动物实验 |
|---|
| 动物模型 | Primary human-tumor xenograft models in NU/J6-week old female mice |
| 配制 | PBS |
| 剂量 | 100 mg/kg per os daily for 21 days |
| 给药处理 | oral gavage |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0662 mL | 10.3308 mL | 20.6616 mL |
| 5 mM | 0.4132 mL | 2.0662 mL | 4.1323 mL |
| 10 mM | 0.2066 mL | 1.0331 mL | 2.0662 mL |
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