Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR).
The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.
['Ramachandran|Sreekanth A|SA|', 'Jadhavar|Pradeep S|PS|', 'Singh|Manvendra P|MP|', 'Sharma|Ankesh|A|', 'Bagle|Gaurav N|GN|', 'Quinn|Kevin P|KP|', 'Wong|Po-Yin|PY|', 'Protter|Andrew A|AA|', 'Rai|Roopa|R|', 'Pham|Son M|SM|', 'Lindquist|Jeffrey N|JN|']
D064007:Ataxia Telangiectasia Mutated Proteins D004353:Drug Evaluation, Preclinical D006801:Humans D020128:Inhibitory Concentration 50 D019869:Phosphatidylinositol 3-Kinases D011485:Protein Binding D047428:Protein Kinase Inhibitors D017346:Protein Serine-Threonine Kinases D011720:Pyrazoles D011725:Pyridines D011743:Pyrimidines
Pyrazolopyrimidine ATR DNA damage HTS PI3K