NU6027

Names

[ CAS No. ]:
220036-08-8

[ Name ]:
NU6027

[Synonym ]:
6-(Cyclohexylmethoxy)-5-nitroso-2,4-pyrimidinediamine
4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine
2,6-Diamino-4-cyclohexylmethoxy-5-nitroso pyrimidine
NU6027
NW1
1e1x
6-CYCLOHEXYLMETHYLOXY-5-NITROSO-PYRIMIDINE-2,4-DIAMINE
2,4-Pyrimidinediamine, 6-(cyclohexylmethoxy)-5-nitroso-

Biological Activity

[Description]:

NU6027 is a potent and ATP-competitive inhibitor of both CDK1 and CDK2, with Kis of 2.5 µM and 1.3 µM, respectively. NU6027 is also a potent inhibitor of ATR and enhances hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner[1][2].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> ATM/ATR

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Signaling Pathways >> PI3K/Akt/mTOR >> ATM/ATR

[Target]

CDK1:2.5 μM (Ki)

CDK2:1.3 μM (Ki)

ATR

[In Vitro]

NU6027 (1 nM-100 µM; 48 h) inhibits the growth of human tumor cells with a GI50 of 10±6 µM[1]. NU6027 (0.1-25 µM; 24 h) inhibits ATR activity with an IC50 of 2.8 µM in GM847KD cells. NU6027 (1-10 µM; 24 h) inhibits ATR activity with an IC50 of 6.7±2.3 µM in MCF7 cells[2]. NU6027 (4 or 10 µM; 24 h) attenuates G2/M arrest following DNA damage in MCF7 cells[2]. NU6027 (10 µM; 24 h) significantly reduces RAD51 foci in both control and PF-01367338-treated V-C8 B2 cells[2]. NU6027 (4 µM; 24 h) causes 82% suppression of the increase in RAD51 foci-positive cells treated by PF-01367338[2]. Western Blot Analysis[2] Cell Line: MCF7 cells Concentration: 0, 1, 5, 10 μM Incubation Time: 24 h Result: Inhibited CDK2-mediated pRbT821 by 42±27% compared with 70±12% inhibition of pCHK1S345 with the concentration of 10 µM.

[References]

[1]. Arris CE, et, al. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J Med Chem. 2000 Jul 27; 43(15): 2797-804.

[2]. Peasland A, et, al. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011 Jul 26;105(3):372-81.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
549.2±60.0 °C at 760 mmHg

[ Melting Point ]:
252.5-253.7 °C(lit.)

[ Molecular Formula ]:
C₁₁H₁₇N₅O₂

[ Molecular Weight ]:
251.285

[ Flash Point ]:
286.0±32.9 °C

[ Exact Mass ]:
251.138229

[ PSA ]:
117.21000

[ LogP ]:
3.71

[ Appearance of Characters ]:
lavender

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.699

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: 15 mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Articles

Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells.

PLoS ONE 8 , e57098, (2013)

Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is a key sensor of single-stranded DNA associated with stalled replication forks and repair intermediates generated during DNA repai...

Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines.

Br. J. Cancer 105 , 372-81, (2011)

The ataxia telangiectasia mutated and Rad3-related kinase (ATR) has a key role in the signalling of stalled replication forks and DNA damage to cell cycle checkpoints and DNA repair. It has long been ...

Kinetically-defined component actions in gene repression.

PLoS Comput. Biol. 11(3) , e1004122, (2015)

Gene repression by transcription factors, and glucocorticoid receptors (GR) in particular, is a critical, but poorly understood, physiological response. Among the many unresolved questions is the diff...