WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406385
Description: NU6027 is a potent inhibitor of cellular ATR activity (IC(50)=6.7 μM) and enhanced hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner. NU6027 attenuated G2/M arrest following DNA damage, inhibited RAD51 focus formation and increased the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel. In A2780 cells sensitisation to cisplatin was greatest in cells with functional p53 and mismatch repair (MMR) and sensitisation to temozolomide was greatest in p53 mutant cells with functional MMR. Importantly, NU6027 was synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1. NU6027 inhibits ATR, impairing G2/M arrest and homologous recombination thus increasing sensitivity to DNA-damaging agents and PARP inhibitors. It provides proof of concept data for clinical development of ATR inhibitors.
MedKoo Cat#: 406385
Chemical Formula: C11H17N5O2
Exact Mass: 251.13822
Molecular Weight: 251.28
Elemental Analysis: C, 52.58; H, 6.82; N, 27.87; O, 12.73
Synonym: NU6027; NU-6027; NU 6027.
IUPAC/Chemical Name: 6-(cyclohexylmethoxy)-5-nitrosopyrimidine-2,4-diamine
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)
SMILES Code: NC1=NC(OCC2CCCCC2)=C(N=O)C(N)=N1
1: Peasland A, Wang LZ, Rowling E, Kyle S, Chen T, Hopkins A, Cliby WA, Sarkaria J, Beale G, Edmondson RJ, Curtin NJ. 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. doi: 10.1038/bjc.2011.243. Epub 2011 Jul 5. PubMed PMID: 21730979; PubMed Central PMCID: PMC3172902.
2: Heady L, Fernandez-Serra M, Mancera RL, Joyce S, Venkitaraman AR, Artacho E, Skylaris CK, Ciacchi LC, Payne MC. Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. J Med Chem. 2006 Aug 24;49(17):5141-53. PubMed PMID: 16913703.
3: Mesguiche V, Parsons RJ, Arris CE, Bentley J, Boyle FT, Curtin NJ, Davies TG, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Johnson LN, Newell DR, Noble ME, Wang LZ, Hardcastle IR. 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22. PubMed PMID: 12482427.