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Dinaciclib(SCH727965)

Catalog No.GC17648

Dinaciclib(SCH727965) Chemical Structure

Potent CDK inhibitor

Size Price Stock Qty
10mM (in 1mL DMSO)
$69.00
In stock
5mg
$92.00
In stock
25mg
$249.00
In stock
50mg
$338.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & SDS

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Protocol

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 (pH 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 727965. 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-coated SPA beads. SPA beads were 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 scintillation counter. Dose-response curves were generated from duplicate, eight-point serial dilutions of inhibitory compounds. IC50 values were derived 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 ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

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

Applications

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 experimental 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.

Background

Dinaciclib is a potent cyclin-dependent kinase (CDK) inhibitor with IC50s for CDK2, CDK5, CDK1 and CDK9 at 1 nM, 1 nM, 3 nM, and 4 nM, respectively. [1] It is in phase I or II clinical trials for various cancers.

Dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. [2] Inhibition of CDK 1 suppresses Rb phosphorylation, leading to cell cycle arrest and apoptosis. [3]

Dinaciclib is active against a broad spectrum of human tumor cell lines in vitro and in vivo. It has great potential to improve cancer chemotherapy.

References:
[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.

Chemical Properties

Cas No. 779353-01-4 SDF
Synonyms N/A
Chemical Name 2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol
Canonical SMILES CCC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCCC4CCO
Formula C21H28N6O2 M.Wt 396.49
Solubility ≥ 17.15mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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