NU6027

SKU: orb1300616

Description

NU6027 is a cell-permeable small molecule inhibitor targeting key DNA damage response kinases, with Ki values of 0.4 µM for ATR, 2.5 µM/1.3 µM for CDK1/2, and 2.2 µM for DNA-PK. It is a valuable research tool for studying cell cycle checkpoints and DNA repair mechanisms in both in vitro and in vivo cancer models.

Research Area

Cell Biology, Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 220036-08-8
• MW: 251.29
• Purity: 99.85% (May vary between batches)
• Formula: C₁₁H₁₇N₅O₂
• SMILES: Nc1nc(N)c(N=O)c(OCC2CCCCC2)n1
• Target: ATM/ATR,DNA-PK,CDK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (3.98 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:3 mg/mL (11.94 mM);DMSO:5.5 mg/mL (21.89 mM)

Bioactivity

• Target IC50:
  CDK2:1.3 μM(Ki)|DNA-PK:2.2 μM(Ki)|ATR:0.4 μM(Ki)|CDK1:2.5 μM(Ki)
• In Vitro:
  NU6027 is soaked into crystals of monomeric CDK2 and the structure refined to a resolution of 1.85 . NU6027 (100 μM) 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. 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 2 gy 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. 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.
• Cell Research:
  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. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

DNAPK, DNA-PK, Cyclin dependent kinase, cytotoxicity, CDK1, CDK, CDK2, cisplatin, cancer, Ataxia telangiectasia mutated, ATM, ATM/ATR, ATM and RAD3 related, ATR, NU 6027, NU6027, NU-6027, inhibit, Inhibitor, hydroxyurea

Compound Identifiers

PubChem CID

398148