The Broad Institute, Inc.

Dana-farber-cancer Institute Inc.

Bayer Pharma Aktiengesellschaft

Bayer Aktiengesellschaft

Heidi Greulich

Matthew Meyerson

Xiaoyun Wu

Timothy A Lewis

Philip Lienau

Martin Lange

Alex Burgin

Detlev Sülzle

Manuel Ellermann

Charlotte Christine Kopitz

Adrian Tersteegen

Knut Eis

Stefan Nikolaus Gradl

Antje Margret Wengner

Ulrike Sack

Christa Hegele-Hartung

Monica Schenone

Luc De Waal

Stephan Siegel

Daniel Korr

Bethany Kaplan

Ulrich Klar

Ulf Bömer

Benito Munoz

Markus Berger

Volker Schulze

Ursula Mönning

Kirstin Petersen

Keith Graham

Dieter Moosmayer

Jens Schröder

Franziska Siegel

Michael Niehues

Uwe Eberspächer

Lara Nicole Gechijian

Phi Manh Dinh

Hassan Youssef Harb

Lucian De Waal

Ulricke Sack

Eis Knut

Timothy Lewis A

The present invention includes name compounds of general formula (I): (I) in which R, R, Rand Rare as defined herein, methods for their preparation, pharmaceutical compositions and combinations comprising said compounds, and their use for the treatment of hyperproliferative diseases.

1,2,4-triazin-3(2H)-one compounds for the treatment of hyperproliferative diseases

Compounds of formula (I) for use in the treatment or prophylaxis of a disease, which is a hyperproliferative disease and/or a disorder responsive to induction of cell death, selected from a haematological tumour, a solid tumour and/or metastases thereof, said tumour harbouring a mutant EGFR with exon 19 or 21 mutations, and their use as pharmaceuticals.

4H-pyrrolo[3,2-c]pyridin-4-one derivatives

The present disclosure features methods for identifying pateints having a hyperproliferative disease, disorder, or condition responsive to phosphodiesterase 3 (PDE3) and schlafen family member 12 (SLFN12) complex formation. The hyperproliferative disease, disorder, or condition may be cancer in a patient including glioblastoma, melanoma, ovarian cancer, cervical cancer, sarcoma, or hematopoietic cancers, such as acute myeloid leukemia. Those responsive diseases, disorders, or conditions may be identified using the biomarker AIP and/or TRRAP in combination with those biomarkers pertinent to phosphodieseterase 3 and schlafen family member 12 complexes which may be formed by PDE3 modulation with certain active compounds. Expression of combinations of these biomarkers have been shown to correlate with active compound (e.g., PDE3 modulator, PDE3A modulator, PDE3B modulator) sensitivity.

Identification of PDE3 modulator responsive cancers

The present invention provides dihydrooxydiazinone compounds of general formula (I): in which R, R, R, and R, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.

Dihydrooxadiazinones

The present invention features improved compounds, especially methods of identifying patients having cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).

Compounds, compositions and methods for cancer patient stratification and cancer treatment

The present invention provides dihydrooxydiazinone compounds of general formula (I) in which R, R, R, and R, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.

The present invention provides dihydrooxydiazinone compounds of general formula (I): in which R, R, R, and R, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients. 

Compounds of formula (I) processes for their production and their use as pharmaceuticals. 

The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).

Compositions and methods for cancer expressing PDE3A or SLFN12

The present invention features improved compounds, especially the compound having the structure (1). Compositions and methods of identifying patients having cancer using biomarkers (e.g., PDE3A, PDE3B, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention. 

Compounds, compositions and methods for cancer treatment

The present invention features improved Compounds, especially (I) methods of identifying patients having Cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein). 

Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.

Compounds and compositions for the treatment of cancer

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Cambridge, MA, United States of America

Heidi Greulich