Vertex Pharmaceuticals, Inc.

The University of Newcastle Upon Tyne

John Robert Pollard

Philip Michael Reaper

Mohammed Asmal

Tao Chen

Nicola Curtin

Susanna Falcon

Fiona Middleton

Scott Fields

Peter Littlewood

Scott Zachary Fields

Fiona Kay Middleton

Nicola Jane Curtin

Described herein are methods of treating a proliferative disorder (e.g., cancer) in a patient by administering a DNA damaging agent and between about 12 and about 48 hours later administering to the subject a compound that inhibits ATR protein kinase. Methods of treating a proliferative disorder (e.g., cancer) in a patient by administering a compound that inhibits ATR protein kinase are also described. Exemplary ATR inhibitors are represented by Formulae A-I and A-II or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein. 

Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors

The present invention relates to compounds useful as inhibitors of ATR protein kinase and combination therapies thereof. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

Compounds useful as inhibitors of ATR kinase and combination therapies thereof

This invention relates to methods and compositions for treating pancreatic cancer. More specifically, this invention relates to treating pancreatic cancer with certain ATR inhibitors in combination with gemcitabine and/or radiation therapy. This invention also relates to methods and compositions for treating non-small cell lung cancer. More specifically, this invention relates to treating non-small cell lung cancer with an ATR inhibitor in combination with cisplatin or carboplatin, etoposide, and ionizing radiation.

Treating cancer with ATR inhibitors

The present relates to methods for detecting DNA damage in subjects treated with an ATR inhibitor. More specifically, this invention relates to a method for measuring changes in levels of &#x3b3;H2AX and/or pChk1in, e.g., surrogate tissue cells, following ex vivo stimulation with a DNA damaging agent.

Method for measuring ATR inhibition mediated increases in DNA damage

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Abingdon, United Kingdom

John Robert Pollard