Dinaciclib

Catalog No.S2768 Batch:S276808

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Technical Data

Formula

C21H28N6O2
Molecular Weight 396.49 CAS No. 779353-01-4
Solubility (25°C)* In vitro DMSO 79 mg/mL (199.24 mM)
Ethanol 35 mg/mL (88.27 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O
25.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 500 mg/mL clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify; add 50 μL Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Dinaciclib 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. Dinaciclib induces apoptosis through the activation of caspases 8 and 9. Phase 3.
Targets
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
In vitro 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. [1] Addition of Dinaciclib during hydroxyurea exposure also suppresses accumulation of γ-H2AX, in a dose-dependent manner. [2] Dinaciclib inhibits melanoma cell proliferation, and drives melanoma cells into massive apoptosis. [3] 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. [4]
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. [1]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    A2780 cells

  • Concentrations

    0 μM -5 μM

  • Incubation Time

    24 hours

  • Method

    A2780 cells are maintained in DMEM plus 10% fetal bovine serum and passaged twice weekly by detaching the monolayer with trypsin-EDTA. One hundred microliters of A2780 cells (5 × 103 cells) are added per well to a 96-well Cytostar-T plate and incubated for 16 hours to 24 hours at 37 °C. Dinaciclib is serially diluted in complete media plus 2% 14C-labeled dThd. Media are removed from the Cytostar T plate; 200 μL of various Dinaciclib dilutions are added in quadruplicate; and the cells are incubated for 24 hours at 37 °C. Accumulated incorporation of radiolabel is assayed using scintillation proximity and measured on a TopCounTM.
Animal Study:[1]
  • Animal Models

    Nude mice bearing A2780 tumors

  • Dosages

    8 mg/kg, 16 mg/kg, 32 mg/kg, and 48 mg/kg

  • Administration

    Administered via i.p.

Customer Product Validation

Data from [Data independently produced by Genes Cancer, 2014, 5(7-8), 261-72]

, , Oncogene, 2017, 36(23):3263-3273

,

Data from [Data independently produced by , , Mol Carcinog, 2018, 57(4):469-482]

Selleck's Dinaciclib has been cited by 141 publications

The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study [ Cells, 2024, 13(5)368] PubMed: 38474332
PIK Your Poison: The Effects of Combining PI3K and CDK Inhibitors against Metastatic Cutaneous Squamous Cell Carcinoma In Vitro [ Cancers (Basel), 2024, 16(2)370] PubMed: 38254859
The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells [ World J Oncol, 2024, 15(2):192-208] PubMed: 38545471
Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs) [ Research Square, 2024, 10.21203/rs.3.rs-3857577/v1] PubMed: none
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8] PubMed: 36736316
Yolk granule fusion and microtubule aster formation regulate cortical granule translocation and exocytosis in zebrafish oocytes [ PLoS Biol, 2023, 21(6):e3002146] PubMed: 37289834
FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation [ Oncogene, 2023, 42(39):2878-2891] PubMed: 37596321
FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation [ Oncogene, 2023, 10.1038/s41388-023-02809-0] PubMed: 37596321
SETD2 regulates chromatin accessibility and transcription to suppress lung tumorigenesis [ JCI Insight, 2023, 8(4)e154120] PubMed: 36810256
Kinome-wide CRISPR-Cas9 knockout screens revealed PLK1 as a therapeutic target for osteosarcoma [ Cell Death Discov, 2023, 9(1):231] PubMed: 37419907

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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