Dinaciclib (SCH727965)_CDK抑制剂_779353-01-4_Apexbio

Dinaciclib (SCH727965)

Evaluation Sample

客户使用Apexbio产品发表的文献

质量控制

质量控制和MSDS

COA (Certificate Of Analysis)

HPLC

NMR (Nuclear Magnetic Resonance)

MSDS (Material Safety Data Sheet)

Western Blot data of dinaciclib treated 1205Lu cells treated

with 30 nM of dinaciclib for increasing periods of time (0–

48 hrs). Along with a decrease in pRBser807/811,

dinaciclib induced a marked upregulation of p53, increase

in cleaved caspase-3, and down regulation of the pro-

survival molecules Bcl-2, XIAP, and Mcl-1. The membrane

was probed for actin expression to ensure equal protein

相关生物数据

化学性质

CAS号779353-01-4SDF Download SDF

化学名2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol SMILES CCC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCCC4CCO

分子式C21H28N6O2分子量396.49

溶解性Soluble in DMSO > 10 mM储存条件Store at -20°C

一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。储液可以在零下20℃中保存数月。

运输条件试用装:蓝冰运输。

其他可选规格:常温运输或根据您的要求用蓝冰运输。

生物活性

描述Dinaciclib (SCH727965)是一种新型有效的CDK抑制剂,作用于CDK2、CDK5、CDK1和CDK9,IC50值分别为1 nM、1 nM、3 nM和4 nM。靶点CDK2CDK5CDK1CDK9

IC50 1 nM 1 nM 3 nM 4 nM

实验操作

Kinase experiment [1]:

Cyclin/CDK kinase assay Recombinant cyclin/CDK holoenzymes were purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK . Cyclin/CDK complexes were typically diluted to a final concentration of 50 μg/mL in a kinase reaction buffer containing 50 mmol/L Tris-HCl (p H 8.0), 10 mmol/L MgCl2, 1 mmol/L DTT, and 0.1 mmol/L sodium orthovanadate. For each kinase reaction, 1 μg of enzyme and 20 μL of a 2-μmol/L substrate solution (a biotinylated peptide derived from histone H1; Amersham) were mixed and combined with 10 μL of diluted SCH 72 7965. The reaction was started by the addition of 50 μL of 2 μmol/L ATP and 0.1 μCi of 33P-ATP. Kinase reactions were incubated for 1 hour at room temperature and were stopped by the addition of 0.1% Triton X-100, 1 mmol/L ATP, 5 mmol/L EDTA, and 5 mg/mL streptavidin-coate

d SPA beads. SPA beads wer

e captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads were washed twice with

2 mol/L NaCl and twice with 2 mol/L NaCl containing 1% phosphoric acid. The signal was then assayed using a Top-Count 96-well liquid scinti llation counter. Dose-response curves were generated from duplicate, eight-point serial dilutions of inhibitory compounds. IC50 values were d erived by nonlinear regression analysis.

Cell experiment [1]:

Cell lines A2780 cells

Preparation method Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultraso nic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition 2 h

Applications SCH 727965 significantly abrogates phosphorylation of Rb on Ser 807/811 at concentrations >6.25 nmol/L and also leads to the generation of the p85 PARP cleavage product. 100 nmol/L SCH727965 treatment for 2 hours is effective in inducing suppression of Rb phosphorylation and caspase activation which can be detected up to 6 hours later.

Animal experiment [1]:

Animal models A2780 ovarian cancer mouse xenograft model Dosage form i.p. administration at 8, 16, 32, and 48 mg/kg daily

Application SCH 727965 i.p. administration at 8, 16, 32, and 48 mg/kg daily for 10 days shows tumor inhibitionby 70%, 70%, 89%, and 96%, respectively. SCH 727965 is also well tolerated, and the maximum body weight loss in the highest dosage group is 5%.

Other notes Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an ex perimental system error and it is normal.

References:

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

产品描述

Dinaciclib是一种有效的细胞周期蛋白依赖性激酶(CDK)抑制剂,作用于CDK2、CDK5、CDK1和CDK9,IC50值分别为1 nM、1 nM、3 nM和4 nM[1]。Dinaciclib目前正处于I/II期临床研究中,用于治疗各种癌症。

Dinaciclib也可以与bromodomains的乙酰化赖氨酸识别位点相互作用[2]。抑制CDK1可以抑制Rb的磷酸化,导致细胞周期停滞和细胞凋亡[3]。在体外和体内,Dinaciclib可以抑制一系列人体肿瘤细胞的生长。Dinaciclib具有很大的潜力可以提高癌症化疗的效果。

参考文献:

[1]Parry D. , et al. (2010). Dinaciclib (SCH 727965), a Novel and Potent Cyclin-Dependent Kinase Inhibitor. Mol Cancer Ther (9): 2344- 2353.

[2]Martin, M. P., et al. (2013). Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chemical Biology 8 (11): 2360–5.

[3]Payton M. , et al. (2006). Discovery and Evaluation of Dual CDK1 and CDK2 Inhibitors. Cancer Res 66: 4299-4308.