title: Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer.
abstract: In this article, we review the ATR inhibitor field from initial pharmacological tools to first-generation clinical candidates with the potential to bring benefit to cancer patients. ATR is a critical part of the cell DNA-damage response. Over the past decade or more, compounds with weak ATR potency and low specificity have been used as tools in early studies to elucidate ATR pharmacology. More recently highly potent, selective and in vivo active ATR inhibitors have been developed enabling detailed preclinical in vitro and in vivo target assessment to be made. The published studies reveal the potential of ATR inhibitors for use as monotherapy or in combination with DNA-damaging agents. To date, VX-970 and AZD6738, have entered clinical assessment.
authors.affiliation: AstraZeneca, Unit 310 - Darwin Building, Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Foote
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Lau
authors.affiliation: AstraZeneca, Unit 310 - Darwin Building, Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
authors.forename: J Willem M
authors.initials: JW
authors.lastname: Nissink
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy*; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007555:Isoxazoles; D011719:Pyrazines; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000598331:berzosertib