Sugen Incorporated

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Other

University of California

Bio-signal Corporation Ltd.

Klaus Peter Hirth

Peng Cho Tang

Laura Kay Shawver

Gerald McMahon

Elaina Mann

Aviv Gazit

Li Hsiang Sun

Axel Ullrich

Reiner Lammers

Istvan Szekely

Janis Haimichael

Jianming Tsai

Alex Levitzki

Donna Pruess Schwartz

Hui Chen

Tamas Bajor

Alexander Levitzki

Gyorgi Keri

Jingrong Jean Cui

Congxin Liang

Dennis J Slamon

Chung Chen Wei

Fairooz F Kabbinavar

Harald App

Connie Li Sun

Annie Fong

Blair Narog

Laura K Shawyer

The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers characterized by over-activity or inappropriate activity HER2 or EGFR.

Method and compositions for inhibiting cell proliferative disorders

The present invention relates to organic molecules capable of modulating, regulating and/or inhibiting protein kinase signal transduction. Such compounds are useful for the treatment of diseases related to unregulated protein kinase signal transduction, including cell proliferative diseases such as cancer, atherosclerosis, arthritis and restenosis and metabolic diseases such as diabetes. The present invention features indolinone compounds that potently inhibit protein kinases and related products and methods. Inhibitors specific to the FLK protein kinase can be obtained by adding chemical substituents to the 3-[(indole-3-yl)methylene]-2-indolinone, in particular at the 1' position of the indole ring. Indolinone compounds that specifically inhibit the FLK and platelet derived growth factor protein kinases can harbor a tetrahydroindole or cyclopentano-b-pyrrol moiety. Indolinone compounds that are modified with substituents, particularly at the 5 position of the oxindole ring, can effectively activate protein kinases. This invention also features novel hydrosoluble indolinone compounds that are tyrosine kinase inhibitors and related products and methods.

Indolinone combinatorial libraries and related products and methods for the treatment of disease

This invention relates to 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors. Particular 4-substituted 7-aza-indolin-2-ones disclosed herein are of Formula 1and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R, R, R, R, X, Y, and Z are defined herein. The invention further relates to pharmaceutical compositions and dosage forms comprising compounds of Formula 1 and to methods of their use for the treatment and/or prevention of diseases such as, but not limited to, cancer.

4-substituted 7-AZA-indolin-2-ones and their use as protein kinase inhibitors

The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.

The present invention relates to methods for treating diseases and disorders related to unregulated angiogenesis and/or vasculogenesis. More specifically, this invention relates to methods for treating diseases and disorders, such as rheumatoid arthritis, endometriosis, ocular neovascularization, solid tumor growth and metastases, and excessive scarring during wound healing, with indolinone compounds.

Methods for treating diseases and disorders related to unregulated angiogenesis and/or vasculogenesis

The present invention relates to novel 3-(piperazinyl-benylidenyl)-2-indolinone compounds and derivatives and physiologically acceptable salts thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.

3-(piperazinylbenzylidenyl)-2-indolinone compounds and derivatives as protein tyrosine kinase inhibitors

The present invention relates to novel heteroaryl-carboxamides which modulate the activity of protein tyrosine kinases and therefore are expected to be useful in the treatment of abnormal protein tyrosine kinase activity driven disorders including cancer.

Heteroarylcarboxamide compounds active against protein tyrosine kinase related disorders

4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors

Methods and compositions for inhibiting cell proliferative disorders

The present invention concerns compounds which can inhibit platelet derived growth factor receptor (PDGF-R) activity, preferably such compounds also inhibit the activity other members of the PDGF-R super family and are selective for members of the PDGF-R super family. The PDGF-R super family includes PDGF-R and PDGF-R related kinases Flt, and KDR. The featured compounds are active on cell cultures to reduce the activity of the PDGF-R and preferably one or more PDGF-R related kinases. An example of a featured compound, A10 (see FIG.,), and its ability to inhibit growth of tumor cells in vivo is described below. Using the present application as guide other compounds able to inhibit PDGF-R and preferably Flt and/or KDR can be obtained. Such compounds are preferably used to treat patients suffering from cell proliferative disorders characterized by inappropriate PDGF-R activity.

Treatment of platelet derived growth factor related disorders such as cancers

The present invention relates to novel isoxazole-4-carboxamides which modulate the activity of protein tyrosine kinases and therefore are expected to be useful in the treatment of abnormal protein tyrosine kinase activity driven disorders including cancer.

Isoxazole-4-carboxamide compounds active against protein tryosine kinase related disorders

Indolinone combinatorial libraries and related products and methods for

This invention is directed to methods and compositions for treating hyperproliferative skin disorders utilizing a quinazoline derivative as an active ingredient.

Psoriasis treatment with quinazoline compounds

The present invention concerns compounds which can inhibit platelet derived growth factor receptor (PDGF-R) activity, preferably such compounds also inhibit the activity other members of the PDGF-R super family and are selective for members of the PDGF-R super family. The PDGF-R super family includes PDGF-R and PDGF-R related kinases Flt, and KDR. The featured compounds are active on cell cultures to reduce the activity of the PDGF-R and preferably one or more PDGF-R related kinases. An example of a featured compound, A10 (see FIG. 1a), and its ability to inhibit growth of tumor cells in vivo is described below. Using the present application as guide other compounds able to inhibit PDGF-R and preferably Flt and/or KDR can be obtained. Such compounds are preferably used to treat patients suffering from cell proliferative disorders characterized by inappropriate PDGF-R activity.

Treatment of platelet derived growth factor related disorders such as

The present invention concerns compounds which can inhibit platelet derived growth factor receptor (PDGF-R) activity, preferably such compounds also inhibit the activity other members of the PDFG-R superfamily and are selective for members of the PDGF-R superfamily. The PDGF-R superfamily includes PDGF-R and PDGF-R related kinases Flt, and KDR. The featured compounds are active on cell cultures to reduce the activity of the PDGF-R and preferably one or more PDGF-R related kinases. An example of a featured compound, A10 (see FIG. 1a), and its ability to inhibit growth of tumor cells in vivo is described below. Using the present application as guide other compounds able to inhibit PDGF-R and preferably Flt and/or KDR can be obtained. Such compounds are preferably used to treat patients suffering from cell proliferative disorders characterized by inappropriate PDGF-R activity.

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San Francisco, CA, United States of America

Klaus Peter Hirth