Calcimedica, Inc.

Merck + Co., Inc.

The United States Government As Represented by the Department of Veterans Affairs

Neurogenetic Pharmaceuticals, Inc.

Calcimedia, Inc.

Va Medical Center

Kenneth Stauderman

Gonul Velicelebi

Jack Roos

Jeffrey Paul Whitten

Yazhong Pei

Michael Dunn

Jianguo Cao

Jonathan Bryant Grey

Evan W Rogers

Brian Dyck

Zhijun Wang

Kari Lynn Ohlsen

Paul J Digregorio

Soan Cheng

David P M Pleynet

Michael Miller Harpold

Mark E Williams

Elizabeth J Ackermann

Steve V Wagner

Maria Z Kounnas

Sudarshan Hebbar

Midori Yenari

Rachid Kacimi

Frank King

Compositions and methods related to the amelioration of pancreatitis through the pharmaceutical manipulation of calcium signaling are disclosed. Such compositions and methods may be used to ameliorate symptoms of acute or chronic pancreatitis or to reduce the chance or severity of pancreatitis in an individual at risk of the condition. In other embodiments, disclosed herein are compositions and methods related to the amelioration of viral diseases through the pharmaceutical manipulation of calcium signaling. In further embodiments, disclosed herein are compositions and methods related to the amelioration of Th17-induced diseases through the pharmaceutical manipulation of calcium signaling.

Pyrazine-containing compound

Pancreatitis treatment

Described herein are methods of treatment of stroke and traumatic brain injury comprising administration of a CRAC channel inhibitor.

Use of CRAC channel inhibitors for the treatment of stroke and traumatic brain injury

In accordance with the present invention, it has been discovered that compounds which modulate the &#x3b3;-secretase enzyme to make more of the shorter, less toxic and less aggregation-prone A&#x3b2; peptides (such as A&#x3b2;37 and A&#x3b2;38), while making less of the longer and more toxic and aggregation-prone AB peptides (such as AB40 and AB42) are useful as gamma-secretase modulators. In addition, these GSM compounds have further been discovered to have the selective property of modulating the formation of various AB peptides, while not inhibiting the overall activity of the &#x3b3;-secretase enzyme. Thus, such compounds do not impede other critical functions of the &#x3b3;-secretase enzyme, such as generating fragments from Notch that appear to control gene expression and cell differentiation. Therefore, in accordance with the present invention, there are provided screening assays useful for determining whether test compounds have GSM activity; accordingly, invention assays facilitate the identification of new gamma-secretase modulators. Such screening assays can be performed in a variety of ways, e.g., by assessing whether test compounds: lower the level of A&#x3b2;42 peptide, increase the level of A&#x3b2;37 and/or A&#x3b2;38 peptides, have substantially no effect on the processing of other &#x3b3;-secretase substrates, and/or interact with at least one component of the &#x3b3;-secretase complex. Also provided in accordance with the present invention are compounds having gamma-secretase modulatory activity as identified by any of the methods described herein; methods for producing formulations useful for modulating gamma-secretase activity, as well as the resulting formulations; methods for modulating gamma-secretase activity employing compounds identified according to invention methods and/or invention formulations, and the like.

Gamma-secretase modulatory compounds, methods for identifying same, and uses therefor

Described herein are compounds and pharmaceutical compositions containing compounds of Formula (I), which modulate the activity of store-operated calcium (SOC) channels: wherein R, Rand Rare defined herein. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Compounds that modulate intracellular calcium

Described herein are compositions and uses thereof related to Carelease-activated Ca(CRAC) channel activity. Also described herein CRAC channel modulators for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Calcium channel proteins and uses thereof

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases, disorders or conditions that would benefit from inhibition of SOC channel activity.

Described herein are compounds of Formula (I): 

Trisubstituted thiophenes that modulate intracellular calcium

Described herein are compounds of Formula (I): wherein A, J, Z, X, Rand Rare defined herein, and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Methods are provided for identifying agents that modulate intracellular calcium. Also provided are methods of modulating calcium within cells and methods of identifying proteins involved in modulating intracellular calcium.

Methods of modulating and identifying agents that modulate intracellular calcium

Described herein are compounds of Formula I and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also describe herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

Growing community of inventors

San Diego, CA, United States of America

Kenneth Stauderman