NU6027

Alias: NU-6027; NU 6027; NU6027
Cat No.:V1546 Purity: ≥98%
NU6027 (NU-6027; NU 6027) is a novel, potent and ATP competitive ATR/CDK (ataxia telangiectasia and Rad3-related/Cyclin-dependent kinases) inhibitor with potential antitumor activity.
NU6027 Chemical Structure CAS No.: 220036-08-8
Product category: CDK
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

NU6027 (NU-6027; NU 6027) is a novel, potent and ATP competitive ATR/CDK (ataxia telangiectasia and Rad3-related/Cyclin-dependent kinases) inhibitor with potential antitumor activity. At 2.5 μM/1.3 μM, 0.4 μM, and 2.2 μM, it inhibits CDK1/2, ATR, and DNA-PK.

Biological Activity I Assay Protocols (From Reference)
Targets
ATR (IC50 = 0.4 μM); CDK2 (IC50 = 1.3 μM); DNA-PK (IC50 = 2.2 μM); CDK1 (IC50 = 2.5 μM)
ln Vitro
Nu6027 is soaked into monomeric CDK2 crystals, and 1.85 Å resolution is achieved in the structure refinement process. The growth of human tumor cells with a mean GI50 of 10 μM is inhibited by NU6027 (100μM). In MCF7 cells, NU6027 reduces the number of cells in S-phase but not in G1 or G2/M.[1] With an IC50 of 6.7 μM in MCF7 cells and 2.8 μM in GM847KD cells, NU6027 is a strong inhibitor of cellular ATR activity. It also increases hydroxyurea and cisplatin cytotoxicity in an ATR-dependent way. At 10 μM, NU6027 inhibits pRbT821 mediated by CDK2 by 42% and pCHK1S345 by 70%. The sensitivity of 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), hydroxyurea (1.8-fold at 4 μM), and cisplatin (1.4-fold at 4 μM and 8.7-fold at 10 μM) against MCF7 cells is significantly increased by NU6027. Additionally, at concentrations above and below their LC50, NU6027 increases the cytotoxicity of camptothecin and temozolomide (a DNA methylating agent) and potentiates 2Gy IR in a concentration-dependent manner. In MCF7 cells, NU6027 (10 μM) increases the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy, but not of the antimitotic drug paclitaxel. It also inhibits the formation of RAD51 foci and attenuates G2/M arrest following DNA damage. When XRCC1 defects in MCF7 cells or inhibition of poly(ADP-ribose) polymerase (PARP) compromise DNA single-strand break repair, NU6027 (4 μM) becomes synthetically lethal.[3] After treating EM-C11 cells for 48 hours, NU6027 (4 μM) raises the percentage of cells in early apoptosis to 7.5% from 1.73% in untreated cells. Comparing XRCC1 deficient OVCAR-4 cells to proficient cells, NU6027 (10 μM) treatment decreases cell survival. When applied to OVCAR-3 cells lacking XRCC1, NU6027 increases the cytotoxicity of cisplatin in comparison to cells with XRCC1. When DSB accumulation is induced by Cisplatin in OVCAR-3 cells lacking XRCC1, NU6027 increases it.[4]
ln Vivo

Cell Assay
Using an enzyme made from starfish oocytes, the inhibition of cyclin B1/CDK1 is measured. The assay buffer consists of 50 mM Tris-HCl pH 7.5 containing 5 mM MgCl2, and a similar procedure is used to determine the inhibition of cyclinA3/CDK2. As for NU6027, the IC50 concentration is the amount needed to inhibit enzyme activity by 50% in the assay conditions employed, and the final ATP concentration in both CDK tests is 12.5 μM. In order to ascertain the Ki values for NU6027 and the Km for ATP for cyclin B1/CDK1 and cyclin A3/CDK2, assays are conducted both with and without NU6027, at two fixed concentrations of NU6027 (5 μM and 10 μM), and with ATP concentrations ranging from 6.25 μM to 800 μM. Regression using unweighted nonlinear least squares is used to fit the data to the Michaelis-Menten equation.
Animal Protocol
The normal 48-hour exposure assay and NU6027 concentrations ranging from 10-9 to 10-4 M are used to assess the growth inhibitory activity of NU6027 in the NCl in vitro cell line panel. The COMPARE algorithm is utilized to examine correlations between the cell growth inhibition profile generated by NU6027 and that of conventional anticancer agents, as well as the well-established CDK inhibitors flavopiridol and olomoucine.
References

[1]. J Med Chem . 2000 Jul 27;43(15):2797-804.

[2]. J Med Chem . 2011 Apr 14;54(7):2320-30.

[3]. Br J Cancer . 2011 Jul 26;105(3):372-81.

[4]. PLoS One . 2013;8(2):e57098.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C11H17N5O2
Molecular Weight
251.28
Exact Mass
251.14
Elemental Analysis
C, 52.58; H, 6.82; N, 27.87; O, 12.73
CAS #
220036-08-8
Appearance
Solid powder
SMILES
C1CCC(CC1)COC2=NC(=NC(=C2N=O)N)N
InChi Key
DGWXOLHKVGDQLN-UHFFFAOYSA-N
InChi Code
InChI=1S/C11H17N5O2/c12-9-8(16-17)10(15-11(13)14-9)18-6-7-4-2-1-3-5-7/h7H,1-6H2,(H4,12,13,14,15)
Chemical Name
6-(cyclohexylmethoxy)-5-nitrosopyrimidine-2,4-diamine
Synonyms
NU-6027; NU 6027; NU6027
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~50 mg/mL (~199 mM)
Water: <1 mg/mL
Ethanol: ~3 mg/mL (~11.9 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.9796 mL 19.8981 mL 39.7962 mL
5 mM 0.7959 mL 3.9796 mL 7.9592 mL
10 mM 0.3980 mL 1.9898 mL 3.9796 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

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

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Biological Data
  • Clonogenic survival assays for CH cells treated with NU6027 (B) and VE-821 (C) at indicated concentrations (see methods for details). PLoS One . 2013;8(2):e57098.
  • FACS read out in CH cells treated with 24 hours of NU6027 is shown here (A). PLoS One . 2013;8(2):e57098.
  • Chemo- and radiosensitisation by NU6027. Br J Cancer . 2011 Jul 26;105(3):372-81.
  • Chemosensitisation and cell cycle effects of NU6027 in ovarian cancer cells with differing p53 and MMR status. Br J Cancer . 2011 Jul 26;105(3):372-81.
  • NU6027 attenuated G2/M arrest and inhibits HR in MCF7 cells and is synthetically lethal with a PARP inhibitor and in XRCC1-defective cells. Br J Cancer . 2011 Jul 26;105(3):372-81.
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