Catalog No.S2768 Synonyms: PS-095760
Molecular Weight(MW): 396.49
Dinaciclib (SCH727965) is a novel and potent CDK inhibitor for CDK2, CDK5, CDK1 and CDK9 with IC50 of 1 nM, 1 nM, 3 nM and 4 nM in cell-free assays, respectively. It also blocks thymidine (dThd) DNA incorporation. Phase 3.
Cited by 8 Publications
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(a) Western blot for RALB-GTP, total RALB and GAPDH proteins in KG1 AML cells treated for 8 h with DMSO or dinaciclib (representative of three independent experiments).
Oncogene, 2017, 36(23):3263-3273. Dinaciclib (SCH727965) purchased from Selleck.
Bcl-xL depleted (Bcl-xL shRNA) or non-target shRNA (NT) carrying LNZ308 and U87 cells were seeded at 60% confluence, allowed to attach overnight, and treated with indicated concentrations of dinaciclib for 24 h. Cytosolic (upper panel) and mitochondrial (lower panel) fractions were prepared, and equal amounts of protein were separated by SDS-PAGE and subjected to Western blotting analysis with the indicated antibodies. Lack of HSP70 in the cytosolic fraction clearly demonstrates that the cytoplasmic cytochrome c, AIF, or smac/DIABLO did not result from the mitochondrial damage during the extraction process.
Mol Carcinog, 2018, 57(4):469-482. Dinaciclib (SCH727965) purchased from Selleck.
(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.
PLoS One, 2017, 12(2):e0172315 . Dinaciclib (SCH727965) purchased from Selleck.
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Choose Selective CDK Inhibitors
|Description||Dinaciclib (SCH727965) is a novel and potent CDK inhibitor for CDK2, CDK5, CDK1 and CDK9 with IC50 of 1 nM, 1 nM, 3 nM and 4 nM in cell-free assays, respectively. It also blocks thymidine (dThd) DNA incorporation. Phase 3.|
Dinaciclib is also a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells with IC50 of 4 nM. Dinaciclib strongly suppresses phosphorylation of Rb on Ser 807/811 at concentrations >6.25 nM, which is in agreement with the observation that 4 nM concentrations are required for 50% inhibition of dThd DNA incorporation in the same cell model. Significantly, complete suppression of Rb phosphorylation is correlated with the onset of apoptosis, as indicated by the appearance of the p85 PARP cleavage product in cells exposed to >6.25 nM Dinaciclib. Dinaciclib is active against a broad spectrum of human tumor cell lines.  Addition of Dinaciclib during hydroxyurea exposure also suppresses accumulation of γ-H2AX, in a dose-dependent manner.  Dinaciclib inhibits melanoma cell proliferation, and drives melanoma cells into massive apoptosis.  Dinaciclib induces the apoptosis of several osteosarcoma cell lines including those resistant to doxorubicin and dasatinib. Dinaciclib attenuates the phosphorylation of RNAP II at serine 2 and the phosphorylation of the CDK inhibitor p27Kip1 at threonine 187. Reductions in phosphorylation activity occurrs at 12 - 40 nM Dinaciclib (4 to 16 hours post-Dinaciclib addition). Dinaciclib also reduces the phosphorylation of Rb at serine 807/811. Dinaciclib induces the apoptosis of mock- and p53-depleted U2OS cells to a similar extent. 
|In vivo||Dinaciclib i.p. administration at 8, 16, 32, and 48 mg/kg daily for 10 days results in tumor inhibition by 70%, 70%, 89%, and 96%, respectively. Dinaciclib MED (minimum effective dose) appears to be <8 mg/kg. Dinaciclib is well tolerated, and the maximum body weight loss in the highest dosage group is 5%. Dinaciclib has dose-dependent antitumor activity in vivo, and that nearly complete inhibition of tumor growth occurs at a dose level below the MTD (maximum tolerated dose). Dinaciclib has a short plasma half-life in mouse. |
Cyclin/CDK kinase assay:Recombinant cyclin/CDK holoenzymes are purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK. Cyclin/CDK complexes are typically diluted to a final concentration of 50 μg/mL in a kinase reaction buffer containing 50 mM Tris-HCl (pH 8.0), 10 mM MgCl2, 1 mM DTT, and 0.1 mM sodium orthovanadate. For each kinase reaction, 1 μg of enzyme and 20 μL of a 2-μM substrate solution (a biotinylated peptide derived from histone H1) are mixed and combined with 10 μL of diluted Dinaciclib. The reaction is started by the addition of 50 μL of 2 μM ATP and 0.1 μCi of 33P-ATP. Kinase reactions are incubated for 1 hour at room temperature and are stopped by the addition of 0.1% Triton X-100, 1 mM ATP, 5 mM EDTA, and 5 mg/mL streptavidin-coated SPA beads. SPA beads are captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads are washed twice with 2 M NaCl and twice with 2 M NaCl containing 1% phosphoric acid. The signal is then assayed using a TopCount 96-well liquid scintillation counter.
|In vitro||DMSO||26 mg/mL warmed (65.57 mM)|
|Ethanol||8 mg/mL warmed (20.17 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03484520||Recruiting||Acute Myeloid Leukemia (AML)||AbbVie|Merck Sharp & Dohme Corp.||July 23 2018||Phase 1|
|NCT01676753||Recruiting||Advanced or Metastatic Breast Cancer|Triple Negative Breast Cancer||Jo Chien|Merck Sharp & Dohme Corp.|University of California San Francisco||June 2016||Phase 1|
|NCT02684617||Recruiting||rrCLL|rrMM|rrDLBCL||Merck Sharp & Dohme Corp.||March 29 2016||Phase 1|
|NCT01783171||Completed||Pancreatic Adenocarcinoma|Recurrent Pancreatic Carcinoma|Stage III Pancreatic Cancer AJCC v6 and v7|Stage IV Pancreatic Cancer AJCC v6 and v7|Unresectable Pancreatic Carcinoma||National Cancer Institute (NCI)||January 15 2013||Phase 1|
|NCT01711528||Completed||Recurrent Plasma Cell Myeloma||National Cancer Institute (NCI)||December 19 2012||Phase 1|
|NCT01650727||Completed||Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma||Merck Sharp & Dohme Corp.||October 2012||Phase 1|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
I want to know how to reconstitute the inhibitor for in vivo studies?
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.