Signal Pharmaceuticals, Inc.

Turning Point Therapeutics, Inc.

Pfizer Corporation

Brion William Murray

Frank Mercurio

Miguel S Barbosa

Hengyi Zhu

Jian Wu Li

Jingrong Jean Cui

Shripad S Bhagwat

Yoshitaka Satoh

Dayong Zhai

Brydon L Bennett

Wei Deng

Anthony M Manning

Eoin C O'Leary

Laura Rodon

Weilin Xie

Merl F Hoekstra

Nathan V Lee

The present disclosure relates to methods and compositions for treating cancer with a diaryl macrocycle in combination with an inhibitor of MAPK/ERK kinase-1 and -2 (MEK1 and MEK2; MAP2K1 and MAP2K2), such as trametinib.

Combination therapy involving diaryl macrocyclic compounds

The present disclosure relates to methods and compositions for treating cancer with a diaryl macrocycle in combination with a KRAS inhibitor, such as an inhibitor of KRAS G12C.

The present invention relates to a method of treating chronic myelogenous leukemia in a subject comprising administering to the subject a compound, such as N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide, that inhibits the T315I mutation in BCR-ABL tyrosine kinase, or a pharmaceutically acceptable salt thereof. The present invention also relates to a pharmaceutical composition comprising a compound such as N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide, that inhibits the T315I mutation in BCR-ABL tyrosine kinase, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide for the treatment of chronic myelogenous leukemia

Compositions and methods are provided for treating NF-&#x3ba;B-related conditions. In particular, the invention provides a stimulus-inducible IKK signalsome, and components and variants thereof. An IKK signalsome or component thereof may be used, for example, to identify antibodies and other modulating agents that inhibit or activate signal transduction via the NF-&#x3ba;B cascade. IKK signalsome, components thereof and/or modulating agents may also be used for the treatment of diseases associated with NF-&#x3ba;B activation.

Double-stranded RNAS directed to IKK-2

Methods are provided for identifying agents that modulate signaling mediated by transforming growth factor beta (TGF-&#x3b2;) and members of the TGF-&#x3b2; family, such as bone morphogenic protein (BMP). Such agents may be identified using screens that evaluate candidate agents for the ability to modulate Smad protein degradation. Agents identified as described herein may be used to augment or inhibit signaling mediated by one or more TGF-&#x3b2; family members in a variety of cell types and for therapeutic purposes.

Methods for modulating signal transduction mediated by TGF-&#x3b2; and related proteins

This invention generally relates to methods for treating or preventing an inflammatory disease or disorder comprising administering to a patient in need thereof an effective amount of a Pyrazoloanthrone Derivative having the following structure: or a pharmaceutically acceptable salt thereof, wherein Rand Rare as defined herein.

Methods for treating inflammatory conditions or inhibiting JNK

Stimulus-inducible protein kinase complex and methods of use therefor

Compounds having activity as selective inhibitors of JNK are disclosed The compounds of this invention are pyrazoloanthrone and derivatives thereof having the following structure: wherein Rand Rare as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Pyrazoloanthrone and derivatives thereof as JNK inhibitors and compositions and methods related thereto

Compositions and methods are provided for treating NF-&kgr;B-related conditions. In particular, the invention provides a stimulus-inducible IKK signalsome, and components and variants thereof. An IKK signalsome or component thereof may be used, for example, to identify antibodies and other modulating agents that inhibit or activate signal transduction via the NF-&kgr;B cascade. IKK signalsome, components thereof and/or modulating agents may also be used for the treatment of diseases associated with NF-&kgr;B activation.

Growing community of inventors

San Diego, CA, United States of America

Brion William Murray