Dinaciclib (SCH727965)

For research use only. Not for use in humans.

目录号:S2768 别名: PS-095760

Dinaciclib (SCH727965) Chemical Structure

Molecular Weight(MW): 396.49

Dinaciclib (SCH727965)是一种新型有效的CDK抑制剂,作用于CDK2CDK5CDK1CDK9,无细胞试验中IC50分别为1 nM,1 nM,3 nM和4 nM。它也会阻断胸甘(dThd) DNA整合。Phase 3。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 2226.36 现货
RMB 1409.03 现货
RMB 3859.45 现货
RMB 5479.23 现货
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客户使用Selleck生产的Dinaciclib (SCH727965)发表文献48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 Dinaciclib (SCH727965)是一种新型有效的CDK抑制剂,作用于CDK2CDK5CDK1CDK9,无细胞试验中IC50分别为1 nM,1 nM,3 nM和4 nM。它也会阻断胸甘(dThd) DNA整合。Phase 3。
特性 [1]
靶点
CDK2 [1]
(Cell-free assay)
CDK5 [1]
(Cell-free assay)
CDK1 [1]
(Cell-free assay)
CDK9 [1]
(Cell-free assay)
1 nM 1 nM 3 nM 4 nM
体外研究

Dinaciclib抑制CDK1和CDK9 效果差不多,但是抑制CDK2和CDK5效果则分别强12和14倍。Dinaciclib作用于A2780细胞,有效抑制的DNA复制,抑制胸甘(dThd)DNA摄入,IC50为4 nM。Dinaciclib 浓度大于6.25 nM时,强抑制Rb在Ser 807/811位点磷酸化。Rb磷酸化的完全抑制与凋亡发生相关,通过用浓度大于6.25 nM 的Dinaciclib处理的细胞中p85 PARP裂解产物的出现来表示。 Dinaciclib有效作用于广谱人肿瘤细胞系。[1] 在羟基脲处理期间加入Dinaciclib,也抑制γ-H2AX累积,这种作用存在剂量依赖性。[2] Dinaciclib 抑制恶性黑色素瘤细胞增殖,使恶性黑色素瘤细胞发生大规模凋亡。[3]Dinaciclib诱导一些骨肉瘤 细胞系凋亡,包括抗Doxorubicin和Dasatinib的细胞。Dinaciclib 降低RNAP II 在 serine 2位点磷酸化,也降低CDK抑制剂p27Kip1在threonine 187位点磷酸化。加入12 nM 到40 nM Dinaciclib处理4小时或16小时,最易使磷酸化作用降低。Dinaciclib也降低Rb在serine 807/811位点磷酸化。Dinaciclib诱导mock-和p53-耗尽的U2OS细胞凋亡,凋亡程度相似。 [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CA46 M3HVVGFxd3C2b4Ppd{BCe3OjeR?= MofXNVAxKG6P MoToNlQhcA>? MmjvbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NUnBdndWOjV{OEm4PFc>
Kasumi-1 MUPBdI9xfG:|aYOgRZN{[Xl? NY\R[GtEOTByIH7N MXiyOEBp MnK0bY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= MY[yOVI5QTh6Nx?=
U937 NGfHelBHfW6ldHnvckBCe3OjeR?= Mof6Nk82NzFyIH7N NXfkb|lyOyCq NYXnPFN1[myxY3vzJIlv\HWldHnvckBw\iC[QmCtNZMh[W6mIHTve45{fHKnYX2geIFz\2W2cx?= NFfW[VEzPDN4MkS2OS=>
8226 MkTlSpVv[3Srb36gRZN{[Xl? M1ztdlIwPS9zMDDuUS=> M4jKeVQhcA>? NWnt[WxI[myxY3vzJIlv\HWldHnvckBw\iC[QmCtNZMh[W6mIHTve45{fHKnYX2geIFz\2W2cx?= M3zOeFI1OzZ{NE[1
H929 MXXGeY5kfGmxbjDBd5NigQ>? NHX3RVUzNzVxMUCgcm0> MXu0JIg> M4i0dIJtd2OtczDpcoR2[3Srb36gc4YhYEKSLUHzJIFv\CCmb4fud5Rz\WGvIIThdodmfHN? NXL4XmxQOjR|NkK0OlU>
K562 MYPGeY5kfGmxbjDBd5NigQ>? NXTuUIl5OS53L{OvPEBvVQ>? M4TCd|YhcA>? Mn3JZoxw[2u|IHnu[JVkfGmxbjDv[kBZSlBvMYOgZY5lKGSxd37zeJJm[W1idHHy[4V1ew>? MYiyOFM3OjR4NR?=
BaF3/Bcr-abl M1fiZ2Z2dmO2aX;uJGF{e2G7 MXmxMlUwOy96IH7N MorxOkBp M3qw[IJtd2OtczDpcoR2[3Srb36gc4YhYEKSLUHzJIFv\CCmb4fud5Rz\WGvIIThdodmfHN? M2\3SFI1OzZ{NE[1
U937  NEDVeFVHfW6ldHnvckBCe3OjeR?= NHzvVIEzNzFyIH7N NWXNfowyOyCq NFnkWXhjdG:la4OgbY5lfWO2aX;uJI9nKFiEUD2xd{BidmRiZH;3cpN1emWjbTD0ZZJo\XS| M4r2RlI1OzZ{NE[1
1205Lu MlzrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrPTG5HOTBxM{Cgcm0> MmLCO|IhcA>? MUTpcohq[mm2czDj[YxtKGe{b4f0bEBidmRic4Xyeol3[Wx? MlK2NlM2Ojd{MkW=
WM1366 MnLIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXhPY1DOTBxM{Cgcm0> NHz3S3c4OiCq MnX5bY5pcWKrdIOgZ4VtdCCpcn;3eIgh[W6mIIP1dpZqfmGu NF25co4zOzV{N{KyOS=>
RD NXXBXmpyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17TU2lEPTB;OD6yJI5O MmLMNlI{OTV{NEC=
Rh41 NVzPW2R6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\ZWnFXUUN3ME2xNE42KG6P Mlm3NlI{OTV{NEC=
Rh18 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlnTTWM2OD1zMD61JI5O NVXKWZZtOjJ|MUWyOFA>
Rh30 NXjBXYt[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTlibl2= MXmyNlMyPTJ2MB?=
BT-12 MlH1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRThwNTDuUS=> MXyyNlMyPTJ2MB?=
CHLA-266 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFnWb4FKSzVyPUeuN{BvVQ>? M4DHNVIzOzF3MkSw
TC-71 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml76TWM2OD1|Lkmgcm0> M1PlflIzOzF3MkSw
CHLA-9 MortS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fPbGlEPTB;ODDuUS=> MkLINlI{OTV{NEC=
CHLA-10 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFy1cGhKSzVyPU[uN{BvVQ>? M37oPFIzOzF3MkSw
CHLA-258 M2e2N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWi5fGs2UUN3ME25Mlkhdk1? NHvsPIIzOjNzNUK0NC=>
GBM2 NYjReFBQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHv4WI1KSzVyPU[uOUBvVQ>? NH;RcpczOjNzNUK0NC=>
NB-1643 M3PS[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1nDRWlEPTB;Mz6zJI5O MWmyNlMyPTJ2MB?=
NB-EBc1 M3;mUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLYTWM2OD15IH7N NXnmTll3OjJ|MUWyOFA>
CHLA-90 NU[3[ZpbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLRc5hKSzVyPUeuOUBvVQ>? MYWyNlMyPTJ2MB?=
CHLA-136 NUL0RpJWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTlwODDuUS=> MYKyNlMyPTJ2MB?=
NALM-6 NHrEbXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2XKZ2lEPTB;ND62JI5O M2f4NVIzOzF3MkSw
COG-LL-317 M3nCZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mm\JTWM2OD14LkWgcm0> NXvyV3UyOjJ|MUWyOFA>
RS4;11 NV7lNpI2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHiWFZKSzVyPUWuNUBvVQ>? NUnBVWhROjJ|MUWyOFA>
MOLT-4 MoLDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoL2TWM2OD17LkOgcm0> M4fXSlIzOzF3MkSw
CCRF-CEM MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEO5cGVKSzVyPUWuOkBvVQ>? NILVTnozOjNzNUK0NC=>
Kasumi-1 NVzCSYp{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3LkXGlEPTB;ND61JI5O M{[2[VIzOzF3MkSw
Karpas-299 M{LmNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mof3TWM2OD1|Lkmgcm0> MoDVNlI{OTV{NEC=
Ramos-RA1 NYHHUW9zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkDzTWM2OD15Lkmgcm0> NXzWcGFEOjJ|MUWyOFA>
MIAPaCa-2 NF7iS2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTST3VxPzJiaB?= M{Tae2dKPTB;MUCgcm0> NV;mc3hJOjF5Nki3O|k>
Pa20C  M{HCSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWS3NkBp NV\jSFlST0l3ME2yNEBvVQ>? MYKyNVc3QDd5OR?=
ML-1 NHzoRWJCeG:ydH;zbZMhSXO|YYm= NVzLUHRMOS1zMECwJI5O NX\C[5NGPCCq NFzYU2tqdmS3Y3XzJIFxd3C2b4Ppd{B{dGmpaITsfS=> MnvPNlE4Pjh5N{e=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Mcl-1 / Bcl-2 / Bcl-xl / Bax / Bak / PUMA / Noxa; 

PubMed: 28714472     


H196 cells treated with doxorubicin for the indicated times were assessed by immunoblot analysis. 

Cleaved PARP / c-Myc; 

PubMed: 25289887     


Immunoblot analysis of A2780 cells during the 5 hr time-course treatment of Dinaciclib (100 nM).

Survivin; 

PubMed: 28207834     


Western blot analysis was performed in cells treated with dinaciclib (25 nM) or vehicle for the indicated time. The levels of Mcl-1, Bcl-xL and survivin were evaluated in BHP7-13, WRO82-1 and 8505C cells.

RNAP II (P-Ser2/P-Ser5); 

PubMed: 25289887     


Immunoblot analysis of A2780 cells during the 5 hr time-course treatment of Dinaciclib (100 nM).

28714472 25289887 28207834
Growth inhibition assay
Cell viability; 

PubMed: 27378523     


(a) Six typical NB cell lines were treated with increasing concentrations of dinaciclib for 48 hrs. Cell viability was then measured by the Cell Counting Kit-8 (CCK-8) assay. P-values < 0.01 (**) or P < 0.001 (***) (Student's t-test, two-tailed) were indicated. (b) The IC50 values of dinaciclib on each cell line listed were calculated based on the data in (a).

Cell viability; 

PubMed: 28361959     


(a-c) The number of cells after dinaciclib treatment. Cell number in 49 fields (7 × 7) was calculated and shown in the graph (n = 4). (a) Total cell number. **p < 0.01 vs control. (b) Number of OCT4 positive cells. **p < 0.01 vs control. (c) Number of OCT4 negative cells. n.s., not significant. (d) The percentage of OCT4 positive cells. **p < 0.01 vs control. *p < 0.05 vs 6 nM.

27378523 28361959
Immunofluorescence
cyclin B1 / α-tubulin / Aurora A; 

PubMed: 28207834     


(B) Cells were treated with dinaciclib (25 nM) or placebo for 24 h and stained with fluorescent antibodies against DAPI (blue), cyclin B1 (red) and α-tubulin (green). Cyclin B1 level was significantly reduced after treatment of dinaciclib in prophase cells of BHP7-13, WRO82-1 and 8505C. (C) Cells were treated with dinaciclib (25 nM) or placebo for 24 h and stained with fluorescent antibodies against DAPI (blue), Aurora A (red) and α-tubulin (green). Aurora A level was significantly reduced after treatment of dinaciclib in BHP7-13, WRO82-1 and 8505C cells in prophase. Scale bar, 10 μm.

OCT4; 

PubMed: 28361959     


Representative images of OCT4 positive cells (red). Nuclei were stained with Hoechst (blue). Scale bars = 200 μm.

28207834 28361959
体内研究 Dinaciclib 每天按8, 16, 32,和48 mg/kg 剂量腹腔注射处理 ,持续10天,导致肿瘤受抑制分别为70%, 70%, 89%,和 96%。Dinaciclib MED(最低有效剂量)约为小于8 mg/kg。Dinaciclib耐药性良好, 且最高剂量处理组中体重损失最高为5%。Dinaciclib 在体内具有抗癌活性,存在剂量依赖性,按低于MTD(最高耐受剂量)的剂量水平处理,几乎完全抑制肿瘤生长。Dinaciclib作用于小鼠,具有短暂的血浆半衰期。[1]

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:[1]
- 合并

Cyclin/CDK激酶实验:

设计从Sf9细胞中纯化的重组cyclin/CDK 全酶,产生表达特定cyclin 或CDK的杆状病毒。 在含 50 mM Tris-HCl (pH 8.0), 10 mM MgCl2, 1 mM DTT,和 0.1 mM原钒酸钠的反应buffer中,Cyclin/CDK 复合体稀释成终浓度为 50 μg/mL。每种激酶反应中, 1 μg酶和 20 μL 2-μM 底物溶液 (组蛋白 H1衍生的一种生物素化的肽段) 混合,然后与10 μL 稀释的Dinaciclib结合。加入 50 μL 2 μM ATP和 0.1 μCi 33P-ATP反应开始。激酶反应在室温下进行1小时,然后加入 0.1% Triton X-100, 1 mM ATP, 5 mM EDTA, 和5 mg/mL 链霉亲和素包被的SPA 磁珠而终止反应。使用96-孔GF/B过滤板和Filtermate广谱收集器 收集SPA 磁珠。用 2 M NaCl 冲洗磁珠两遍,然后用含磷酸的2 M NaCl 再冲洗两遍。使用TopCount 96孔液体闪烁计数器测定信号。
细胞实验:[1]
- 合并
  • Cell lines: A2780细胞
  • Concentrations: 0 μM-5 μM
  • Incubation Time: 24小时
  • Method: A2780 细胞培养在含10%FBS的DMEM培养基上,每周移动两次,通过使用胰蛋白酶-EDTA分离单细胞层。在96孔Cytostar-T板上每孔加入 100 μL A2780细胞 (5 ×103个),然后在37oC下温育16到24小时。Dinaciclib 在含2% 14C标记 dThd的完全培养基上连续稀释。培养基从 Cytostar T板上转移,按一式四份加入200 μL 多种Dinaciclib 稀释液,然后细胞在37oC下温育24小时。使用闪烁亲近法测定,在TopCoun上测量累积的放射性标记物渗透率。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 携带A2780肿瘤的裸鼠
  • Formulation: 20%羟丙基-β-环糊精
  • Dosages: 8 mg/kg, 16 mg/kg, 32 mg/kg,和 48 mg/kg
  • Administration: 腹腔注射
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 26 mg/mL warmed (65.57 mM)
Ethanol 8 mg/mL warmed (20.17 mM)
Water 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):
2% DMSO+30% PEG 300+ddH2O
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 396.49
化学式

C21H28N6O2

CAS号 779353-01-4
储存条件 粉状
溶于溶剂
别名 PS-095760

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

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03484520 Recruiting Drug: Venetoclax|Drug: Dinaciclib Cancer - Acute Myeloid Leukemia AbbVie|Merck Sharp & Dohme Corp. July 23 2018 Phase 1
NCT01434316 Recruiting Drug: Dinaciclib|Drug: Veliparib Advanced Malignant Solid Neoplasm National Cancer Institute (NCI) November 1 2011 Phase 1

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操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    I want to know how to reconstitute the inhibitor for in vivo studies?

  • 回答:

    S2768 (SCH727965) in 15% Captisol at 8 mg/ml is a suspension for oral administration. And it can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution for injection.

CDK Signaling Pathway Map

CDK Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID