Method for measuring ATR inhibition mediated increases in DNA damage
AssigneesVertex Pharmaceuticals Incorporated, University of Newcastle Upon Tyne
InventorsSusanna Falcon, Philip Reaper, John Pollard, Nicola Curtin, Fiona Middleton, Tao Chen
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Abstract
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 γH2AX and/or pChk1Ser345 in, e.g., surrogate tissue cells, following ex vivo stimulation with a DNA damaging agent.
Claims17
A method for monitoring DNA damage in a subject by measuring accumulation of γH2AX in blood, the method comprising:
- a) treating a subject with an ATR inhibitor;
- b) taking blood samples from the subject at various intervals;
- c) treating the blood samples with a DNA damaging agent;
- d) isolating white blood cells from the blood samples;
- and
- e) measuring γH2AX levels in the white blood cells by using antibodies specific for γH2AX, wherein the ATR inhibitor is:
- or a pharmaceutically acceptable salt thereof.
A method for monitoring DNA damage in a subject by measuring changes in γH2AX and/or pChk1Ser345, the method comprising:
- administering an ATR inhibitor to a subject;
- taking surrogate tissue cell samples from the subject at various intervals;
- treating the surrogate tissue cell samples with a DNA damaging agent;
- measuring γH2AX and/or pChk1Ser345 levels in the surrogate tissue cell samples using antibodies specific for γH2AX and/or pChk1Ser345.
Dependencies are inferred from the claim text.