Dinaciclib

产品说明书

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Chemical Structure| 779353-01-4 同义名 : SCH 727965;PS-095760
CAS号 : 779353-01-4
货号 : A196584
分子式 : C21H28N6O2
纯度 : 99%+
分子量 : 396.486
MDL号 : MFCD16037702
存储条件：

Pure form Keep in dark place,Inert atmosphere,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(126.11 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 3.2 mg/mL clear

PO 0.5% CMC-Na 26 mg/mL suspension

生物活性
靶点

  • CDK5

    CDK5, IC50:1 nM

  • CDK2

    CDK2, IC50:1 nM

  • CDK9

    CDK9, IC50:4 nM

  • CDK1

    CDK1, IC50:3 nM
描述 CDK4/6, forming a complex with its partner Cyclin D1/2/3, can mediate the phosphorylation of Rb in G1 cell cycle, as well as stimulating the synthesis cyclin E and D-type cyclins controlled by extracellular mitogens[2]. Dinaciclib can inhibit CDK2, CDK5, CDK1, and CDK9 activity with IC50 values of 1, 1, 3 and 4 nM (measured by Recombinant cyclin/CDK), respectively. Dinaciclib strongly suppressed phosphorylation of Rb on Ser 807/811 at concentrations >6.25 nM for 16h in A2780 cells. Along with that, apoptosis as indicated by the appearance of the p85 PARP cleavage can also be observed. Dinaciclib has broad antiproliferative activity against a wide range of tumor cells, including prostate, breast, colon, SCLC, SCLC, ovarian, pancreatic, melanoma, leukemia, bladder, liver, mantle and lymphoma cell lines, with IC50 ranging from 6-17 nM. Exposure to 250-500 nM of dinaciclib is sufficient to completely suppress DNA synthesis for 24 hours in A2780 cells and that was correlated with the accumulation of apoptosis (sub-G1), which means that short exposures to dinaciclib can induce long-lasting effects in target cells. Intraperitoneal administration of dinaciclib at 8, 16, 32 and 48 mg/kg daily for 10 days resulted in tumor inhibition by 70%, 70%, 89%, and 96%, respectively, in A2780 xenograft mice[1]. Up to now, a lot of clinical trails of dinaciclib treatment for cancer, including ALL, AML, CLL, mantle cell lymphoma, multiple myeloma, melanoma, NSCLC, breast and pancreatic cancer, are undergoing.
作用机制 Dinaciclib can interact with both ATP-binding site and the acetyl-lysine recognition site of bromodomains of CDKs[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
1205Lu 10/30 nM Growth Inhibition Assay 72 h inhibits cell growth and survival 23527225
8226 2/5/10 nM Function Assay 4 h blocks induction of XBP-1s and downstream targets 24362465
BaF3/Bcr-abl 1.5/3/8 nM Function Assay 6 h blocks induction of XBP-1s and downstream targets 24362465
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.52mL

0.50mL

0.25mL

12.61mL

2.52mL

1.26mL

25.22mL

5.04mL

2.52mL
参考文献

[1]Parry D, Guzi T, et al. Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53.

[2]Roskoski R Jr, et al. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacol Res. 2016 May;107:249-275.

[3]Roskoski R Jr, et al. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacol Res. 2016 May;107:249-275.

[4]Martin MP, Olesen SH, et al. Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol. 2013 Nov 15;8(11):2360-5.