NU6027

Catalog No.S7114 Batch:S711401

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Technical Data

Formula

C11H17N5O2
Molecular Weight 251.28 CAS No. 220036-08-8
Solubility (25°C)* In vitro DMSO 50 mg/mL (198.98 mM)
Ethanol 3 mg/mL (11.93 mM)
Water Insoluble
* <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.)

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Biological Activity

Description NU6027 is a potent ATR/CDK inhibitor, inhibits CDK1/2, ATR and DNA-PK with Ki of 2.5 μM/1.3 μM, 0.4 μM and 2.2 μM, enter cells more readily than the 6-aminopurine-based inhibitors.
Targets
ATR [2] CDK2 [1] DNA-PK [2] CDK1 [1]
0.4 μM(Ki) 1.3 μM(Ki) 2.2 μM(Ki) 2.5 μM(Ki)
In vitro NU6027 is soaked into crystals of monomeric CDK2 and the structure refined to a resolution of 1.85 Å. NU6027 (100μM) inhibits growth of human tumor cells with mean GI50 of 10 μM. NU6027 causes a reduction in the number of cells in S-phase but not G1 or G2/M in MCF7 cells. [1] NU6027 is a potent inhibitor of cellular ATR activity with IC50 of 6.7 μM in MCF7 cells and 2.8 μM in GM847KD cells, and enhances hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner. NU6027 (10 μM) inhibits CDK2-mediated pRbT821 by 42% and pCHK1S345 by 70%. NU6027 significantly potentiates sensitivity of cisplatin (1.4-fold at 4 μM and 8.7-fold at 10 μM), doxorubicin (1.3-fold at 4 μM and 2.5-fold at 10 μM), camptothecin (1.4-fold at 4 μM and 2-fold at 10 μM) and hydroxyurea (1.8-fold at 4 μM) aganist MCF7 cells. NU6027 also potentiates 2Gy IR in a concentration-dependent manner and the cytotoxicity of camptothecin and temozolomide (a DNA methylating agent) at concentrations above and below their LC50. NU6027 (10 μM) attenuates G2/M arrest following DNA damage, inhibits RAD51 focus formation and increases the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel in MCF7 cells. NU6027 (4 μM) is synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1 in MCF7 cells. [3] NU6027 (4 μM) increases the proportion of cell in early apoptosis to 7.5% after 48 hours treatment in EM-C11 cells compared to 1.73% in untreated cells. NU6027 (10 μM) treatment reduces survival in XRCC1 deficient OVCAR-4 cells compared to proficient cells. NU6027 enhances cytotoxicity of cisplatin in XRCC1 deficient OVCAR-3 cells compared to XRCC1 proficient cells. NU6027 enhances Cisplatin induced DSB accumulation in XRCC1 deficient OVCAR-3 cells. [4]
Features A more potent inhibitor of cdk1 and cdk2 than NU2058.

Protocol (from reference)

Kinase Assay:

[1]
  • Enzyme Inhibition Studies

    Inhibition of cyclin B1/CDK1 is assayed using enzyme prepared from starfish oocytes. Inhibition of cyclinA3/CDK2 is determined using a similar assay and an assay buffer comprised of 50 mM Tris-HCl pH 7.5 containing 5 mM MgCl2. The final ATP concentration in both CDK assays is 12.5 μM, and the IC50 concentration for NU6027 is the concentration required to inhibit enzyme activity by 50% under the assay conditions used. To determine the Km for ATP for cyclin B1/CDK1 and cyclin A3/CDK2, and Ki values for NU6027, assays are performed in the absence of NU6027 and at two fixed NU6027 concentrations (5 μM and 10 μM), with ATP concentrations ranging from 6.25 μM to 800 μM. Data are fitted to the Michaelis−Menten equation using unweighted nonlinear least squares regression.
Cell Assay:

[1]
  • Cell lines

    human tumor cell lines

  • Concentrations

    ~100 μM

  • Incubation Time

    48 hours

  • Method

    The growth inhibitory activity of the NU6027 is evaluated in the NCl in vitro cell line panel using the standard 48 hours exposure assay and NU6027 concentrations ranging from 10-9 to 10-4 M. Relationships between the profile of cell growth inhibition produced by NU6027 and that of standard anticancer agents, and the established CDK inhibitors olomoucine and flavopiridol, is investigated using the COMPARE algorithm.

Selleck's NU6027 has been cited by 3 publications

The ARID1A-METTL3-m6A axis ensures effective RNase H1-mediated resolution of R-loops and genome stability [ Cell Rep, 2024, 43(2):113779] PubMed: 38358891
Regulation of hypothalamic reactive oxygen species and feeding behavior by phosphorylation of the beta 2 thyroid hormone receptor isoform [ Sci Rep, 2024, 14(1):7200] PubMed: 38531895
PARP1 and CHK1 coordinate PLK1 enzymatic activity during the DNA damage response to promote homologous recombination-mediated repair [ Nucleic Acids Res, 2021, gkab584] PubMed: 34197606

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.