biostudies-literaturePeasland ACancer Research UKNCI NIH HHS372-81https://www.ebi.ac.uk/biostudies/studies/S-EPMC3172902biostudies-literatureUnknown105(3)<h4>Background</h4>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 recognised as an important target for cancer therapy but inhibitors have proved elusive. As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR.<h4>Methods</h4>Cellular ATR kinase activity was determined by CHK1 phosphorylation in human fibroblasts with inducible dominant-negative ATR-kinase dead expression and human breast cancer MCF7 cells. Cell cycle effects and chemo- and radiopotentiation by NU6027 were determined in MCF7 cells and the role of mismatch repair and p53 was determined inBritish journal of cancerIdentification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines.PMC3172902R01 CA148747Hopkins ABeale GPeasland ASarkaria JCurtin NJEdmondson RJWang LZCliby WAKyle SRowling EChen TfalseIdentification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines.<h4>Background</h4>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 recognised as an important target for cancer therapy but inhibitors have proved elusive. As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR.<h4>Methods</h4>Cellular ATR kinase activity was determined by CHK1 phosphorylation in human fibroblasts with inducible dominant-negative ATR-kinase dead expression and human breast cancer MCF7 cells. Cell cycle effects and chemo- and radiopotentiation by NU6027 were determined in MCF7 cells and the role of mismatch repair and p53 was determined in2011-01-01T00:00:00Z2011 Jul2025-04-18T13:21:55.239Z2019-03-27T00:43:55ZS-EPMC31729022173097910.1038/bjc.2011.243