Pfizer Corporation

Cancer Research Technology Limited

Vertex Pharmaceuticals, Inc.

The University of Sheffield

Thomas Helleday

Nicola Curtin

Kumar Sanjiv

The present invention relates to methods of treating cancer in a patient by administering a compound useful as an inhibitor of ATR protein kinase in combination with a compound useful as an inhibitor of Chk1 protein kinase. The aforementioned combination displays a surprising synergistic effect in treating cancer despite the targeted protein kinases being within the same biological pathway. Moreover, the present invention also relates to methods of treating cancer by administering a compound useful as an inhibitor of ATR protein kinase; administering a compound useful as an inhibitor of Chk1 protein kinase; as well as administering a DNA damaging agent to a patient. The compounds utilized in this invention are represented by formula I and formula II: wherein the variables are as defined herein.

Method for treating cancer using a combination of Chk1 and ATR inhibitors

The present invention relates to the use of an agent that inhibits the activity of an enzyme that mediates repair of a DNA strand break in the manufacture of a medicament for the treatment of diseases caused by a defect in a gene that mediates homologous recombination.

Use of RNAI inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer

The invention relates to trycyclic lactam indole derivatives and triacyclic lactam benzimodole derivatives and their use in inhibiting the activity of PARP enzyme. The invention also relates to the use of these compounds in the preparation of medicaments.

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Stockholm, Sweden

Thomas Helleday