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.
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Targets
CDK1, CDK2, ATR, DNAPK
IC50
2.5 μM; 1.3 μM; 0.4 μM; 2.2 μM
Molecular Formula
C11H17N5O2
Chemical Name
2,4-Pyrimidinediamine, 6-(cyclohexylmethoxy)-5-nitroso-
Solubility
DMSO 50 mg/mL; Water <1 mg/mL; Ethanol 3 mg/mL
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. 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.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.
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