Palbociclib (PD0332991) Isethionate

For research use only. Not for use in humans.

Pfizer辉瑞授权生产 目录号:S1579

Palbociclib (PD0332991) Isethionate Chemical Structure

CAS No. 827022-33-3

Palbociclib (PD0332991) Isethionate是一种高度选择性的CDK4/6抑制剂,无细胞试验中IC50为11 nM/16 nM,对CDK1/2/5,EGFR,FGFR,PDGFR, InsR等没有抑制活性。Phase 3。

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客户使用Selleck生产的Palbociclib (PD0332991) Isethionate发表文献240篇:

产品安全说明书

CDK抑制剂选择性比较

生物活性

产品描述 Palbociclib (PD0332991) Isethionate是一种高度选择性的CDK4/6抑制剂,无细胞试验中IC50为11 nM/16 nM,对CDK1/2/5,EGFR,FGFR,PDGFR, InsR等没有抑制活性。Phase 3。
特性 PD 0332991治疗多种癌症,特异性抑制CDK4/6,是第一种有前途的抑制剂。
靶点
CDK4/CyclinD3 [1]
(Cell-free assay)
CDK4/CyclinD1 [1]
(Cell-free assay)
CDK6/CyclinD2 [1]
(Cell-free assay)
9 nM 11 nM 15 nM
体外研究

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。[1]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。PD 0332991诱导MM1.S细胞停滞在G1期,IC50为~0.05 μM。[2]PD 0332991优先抑制Luminal雌激素受体阳性(包括HER2阳性)人类乳腺癌细胞系。PD 0332991作用于大部分敏感的细胞系,促进pRb和cyclin D1基因表达,且降低CDKN2A(p16)基因表达。PD 0332991作用于条件性抗ER抑制的细胞系,增强对Tamoxifen的敏感性。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
H157 NEfUcZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfiUHoxNTFyMDFOwG0> MkTxO|IhcA>? MXnJR|UxRTlizszN NEXHeFQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkO5NFM1Oid-Mk[zPVA{PDJ:L3G+
H2170 NW\IVWdmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnYcnUxNTFyMDFOwG0> NHflemU4OiCq NYn3b|RWUUN3ME21JO69VQ>? MnPmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ|OUCzOFIoRjJ4M{mwN|QzRC:jPh?=
H520 NGniNYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXrV4cxNTFyMDFOwG0> MorFO|IhcA>? NUTLXI9OUUN3ME2wMlc{KM7:TR?= MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjN7MEO0Nkc,OjZ|OUCzOFI9N2F-
H596 NELpOFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWCwMVExOCEQvF2= M2rIe|czKGh? MWnJR|UxRTF{IN88US=> NXuzTo9IRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[zPVA{PDJpPkK2N|kxOzR{PD;hQi=>
IMR-32 MnPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HCXVQ5yqCq NYjVe|VzTE2VTx?= M13J[GlEPTB;Mk[xJI5O NEfWcI09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkKyOVEzOyd-Mk[yNlUyOjN:L3G+
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NGP NIH3ZZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUe0POKhcA>? M{PRSmROW09? MoHiTWM2OD1{LkC3O{DPxE1? NXvLVW5kRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yNlUyOjNpPkK2NlI2OTJ|PD;hQi=>
SH-EP MojDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHruVVg1QMLiaB?= MkXWSG1UVw>? MYTJR|UxRTJwMkGxJO69VQ>? MlLRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{MkWxNlMoRjJ4MkK1NVI{RC:jPh?=
IMR-32 NU[5d2V2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1[5OFEh|ryP MljzNlQhcA>? M2DuV2ROW09? NFjtSIJqdmS3Y3XzJGcyKGG{cnXzeC=> M2HRV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkK1NVI{Lz5{NkKyOVEzOzxxYU6=
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NGP MnXSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUPPZ4dpOSEQvF2= NUHpbFhYOjRiaB?= Mk\mSG1UVw>? MVXpcoR2[2W|IFexJIFzemW|dB?= NWrQUGx5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yNlUyOjNpPkK2NlI2OTJ|PD;hQi=>
SH-EP MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXlNUDPxE1? MlfLNlQhcA>? MmKySG1UVw>? Mk[xbY5lfWOnczDHNUBienKnc4S= NVqwXXp6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yNlUyOjNpPkK2NlI2OTJ|PD;hQi=>
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IMR-32 NITuc5dHfWO2aX;uJGF{e2G7 MkTrNE0yKM7:TR?= NWjHVnVPOjRiaB?= M2XEU2ROW09? MXvy[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:owrDUU3AzSS{EoFPDUmUzNCCjbnVCpHRMOcLiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ? NWfLOJk6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yNlUyOjNpPkK2NlI2OTJ|PD;hQi=>
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U-CH3 MmLsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXTtdYlEOC1zIN88US=> M3nKbFczKGh? MmjXTWM2OD13MjDuUS=> M4XCSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUizPVI2Lz5{NkG4N|kzPTxxYU6=
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U-CH7 MomwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIf0fmIxNTFizszN NHSxNnE4OiCq M4PZWGlEPTB;OUigcm0> MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF6M{myOUc,OjZzOEO5NlU9N2F-
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EoL-1-cell MoHFS5Jwf3SqIFnubIljcXSrb36gZZN{[Xl? MmLoTWM2OCB;IECuNVg4OjZizszN MmnUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg6QTZ|Lze+V2FPT0WUPD;hQi=>
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ES1 M{fpOWdzd3e2aDDJcohq[mm2aX;uJIF{e2G7 NGnCeGZKSzVyIE2gNE4zPTZ{NTFOwG0> MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFk6PjNxJ{7TRW5ITVJ:L3G+
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Rh18 MmjEdWhVWyCjc4PhfS=> M4fvdpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy| MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
RB1 (pT821) / RB1 (pS780); 

PubMed: 30300583     


Immunoblots showing dose-dependent impact of 72 hr palbociclib treatment on indicated protein levels in Kasumi-1 and SKNO-1 cells.

pAMPKα(T172) / AMPKα; 

PubMed: 28453226     


Dose-dependent response of palbociclib on AMPK‐related molecules. HCC cells were treated with different concentrations of palbociclib for 24 h. The phosphorylation of the indicated proteins was determined by western blotting. 

pULK1(S317) / ULK1; 

PubMed: 28453226     


Dose-dependent response of palbociclib on AMPK‐related molecules. HCC cells were treated with different concentrations of palbociclib for 24 h. The phosphorylation of the indicated proteins was determined by western blotting. 

c-Jun / p-c-Jun / NFκB(p50); 

PubMed: 26540629     


The expression of c-Jun and phosphorylated c-Jun was assessed using western blot after the cells were treated with palbociclib. 

p38 / p-P38 / JNK / p-JNK; 

PubMed: 26540629     


MAPK pathway-related proteins, p38, ERK, JNK expression levels were detected.

30300583 28453226 26540629
Growth inhibition assay
Cell viability; 

PubMed: 28453226     


Dose- and time-dependent effects of palbociclib on cell viability in three HCC cell lines. Hep3B, Huh7, and PLC5 cells were treated with palbociclib at the indicated concentrations for 24 or 48 h and assayed by MTT. The solvent (DMSO) concentration in each sample is equal (0.7%).

IC50; 

PubMed: 27099147     


Dose-response curve of ITD+ (red) or control (black) leukemic cells with CDK4/6 inhibitor palbociclib. Cells were incubated with increasing concentrations for 72 hours. Cell viability and proliferation were assessed by using the CTG assay. IC50 values were calculated by using GraphPad Prism software. Error bars indicate ± SEM.

28453226 27099147
Immunofluorescence
γH2AX(Ser139); 

PubMed: 29669860     


Representative maximum‐intensity projections of MCF7 cells treated with the 1 μM palbociclib and/or 7.5 nM bortezomib. Note that 7.5 nM bortezomib inhibits proteasome only partially. Fixed and permeabilized cells were stained with Alexa Fluor 488‐conjugated Ki67 antibody, Alexa Fluor 647‐conjugated phospho‐Histone H2A.X (γH2AX) (pSer139) antibody, and DAPI. All images were acquired with the same magnification, and scale bar is 20 μm.

LC3B; 

PubMed: 28453226     


LC3B immunofluorescence in palbociclib‐treated Hep3B cells. Arrowheads indicate LC3‐positive autophagosomes. Nuclei were counterstained with DAPI (blue). 

29669860 28453226
ELISA
PGE2; 

PubMed: 26540629     


The supernatant of control and 7.5 μM palbociclib-treated cells was collected and stored at −80°C. PGE2 secretion was detected using ELISA.

26540629
体内研究 PD 0332991(150 mg/kg)作用于Colo-205结肠癌移植瘤,诱导肿瘤快速衰退,肿瘤生长相应延迟。PD 0332991(150 mg/kg)作用于MDA-MB-435乳腺癌,诱导全部肿瘤停滞和杀死细胞。PD 0332991(150 mg/kg)处理携带SF-295胶质母细胞瘤,和ZR-75-1乳腺癌和PC-3前列腺肿瘤模型(完全抑制肿瘤生长)的小鼠,显著诱导肿瘤衰退。PD 0332991 (150 mg/kg)处理 MDA-MB-435乳腺癌超过24小时,抑制Rb在Ser780位点磷酸化。PD 0332991(150 mg/kg)处理Colo-205 移植瘤,下调四种E2F调节的基因CDC2, CCNE2, TK1, 和 TOP2A表达。[1]PD 0332991也快速抑制骨髓瘤生长。[2]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[4]
- 合并

CDK活性实验:

在96孔过滤板中进行动力学测评,测定CDK实验的IC50值。所有的CDK-cyclin激酶复合物在昆虫细胞中通过杆状病毒感染而表达,并进行纯化。实验底物是与GST(GST•RB-Cterm)融合的pRb组分(792–928位氨基酸)。总反应体积为0.1 mL,包含终浓度20 mM Tris-HCl,pH 7.4, 50 mM NaCl,1 mM 二硫苏糖醇,10 mM MgCl2,含0.25 μCi[γ-32P]ATP的25 μM ATP(作用于 CDK4-cyclin D1, CDK6-cyclin D2, 和 CDK6-cyclin D3), 20 ng 酶, 1 μg GST•RB-Cterm, 及适度稀释的抑制剂。每孔加入全部组分,除了[γ-32P]ATP,置于混合器中2分钟。加入[γ-32P]ATP开始反应,在25°C下温育15分钟。加入0.1 mL 20% 三氯乙酸终止反应, 实验板置于4°C至少1小时,使底物沉淀。每孔使用 0.2 mL 10%三氯乙酸洗涤 五次,使用β计数器测定渗透的放射性。
细胞实验:[3]
- 合并
  • Cell lines: 人类乳腺癌细胞MDA-MB-435
  • Concentrations: 2 μM
  • Incubation Time: 6 天
  • Method: 细胞按一式两份每孔5,000 到10,000个细胞接种在24孔板中,接种后,加入不同浓度的PD 0332991。对照组不加入药物。温育末期,细胞胰蛋白酶化,并置于等渗溶液中,并立即使用Coulter Z2粒子计数器计数。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 人类结肠癌移植瘤Colo-205
  • Dosages: 150 mg/kg
  • Administration: 每天口服处理
    (Only for Reference)

溶解度 (25°C)

体外 Water 10 mg/mL warmed (17.43 mM)
DMSO Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
saline (with warming)
10mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 573.66
化学式

C24H29N7O2.C2H6O4S

CAS号 827022-33-3
储存条件 粉状
溶于溶剂
别名 N/A

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量