The Queen's Medical Center

Johns Hopkins University

The Queens's Medical Center

Reinhold Penner

Andrea Fleig

Jun O Liu

Curtis R Chong

Fan Pan

Yunzhao Ren

Jonathan R Behr

Andrea Flieg

The invention relates, in part, to methods useful in identifying molecules, that bind TRPM4b, which modulate TRPM4b ion channel activity, and/or which alter expression of TRPM4b within cells. The TRPM4b channels as described herein contain TRPM4b polypeptides, which are in turn encoded by TRPM4b nucleic acids. The ion channels described herein are preferably formed in HEK-293 cells from one or more novel TRPM4b polypeptides, which exhibit one or more of the unique TRPM4b properties described herein.

Methods of screening for TRPM4b modulators

The invention provides methods and compositions for determining the identity of CRACM homologs underlying Icrac activity in cells.

Functional identification of proteins underlying Icrac activity in a cell

The present invention provides compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein each of W, Q, R, R, R, R, R, m, and n is as defined herein, pharmaceutically acceptable compositions thereof, and methods of using the same.

Phenazine derivatives and uses thereof as potassium channel modulators

The present invention relates to the identification and isolation of a novel family of ATP regulated calcium transmembrane channel polypeptides designated herein as 'LTRPC7' (Long Transient Receptor Potential Channel). Channels comprising these polypeptides close in response to concentrations of cytoplasmic ATP in the millimolar range, are subject to inhibition by high intracellular levels of calcium and/or magnesium, and do not respond to depletion or reduction in intracellular calcium stores. The invention further relates to the methods of utilizing LTRPC7 for binding, and the methods for modulating LTRPC7 activity and for measuring LTRPC2 permeability. The invention further relates to the methods of modulating expression of LTRPC7.

Methods of screening for LTRPC7 modulators

The invention relates to methods useful in identifying candidate agents that modulate insulin secretion from an insulin secreting cell, where such molecules modulate TRPM4 activity and expression in the insulin secreting cell.

Methods of screening for TRPM4 modulators of insulin secretion

The present invention provides assays and methods for determining levels of STIM2 activity, thus providing tools for the characterization and study of the regulation of intracellular calcium levels.

Assays and methods for determining STIM2 activity

The invention relates to methods useful in identifying molecules that bind TRPM5, which modulate TRPM5 ion channel activity, and/or which alter expression of TRPM5 within cells. The TRPM5 channels as described herein contain TRPM5 polypeptides, which are in turn encoded by TRPM5 nucleic acids. The ion channels described herein are preferably formed in HEK-293 cells from one or more novel TRPM5 polypeptides, which exhibit one or more of the unique TRPM5 properties described herein.

Methods of screening for TRPM5 modulators

The invention relates, in part, to methods useful in identifying molecules, that bind TRPM4, which modulate TRPM4ion channel activity, and/or which alter expression of TRPM4within cells. The TRPM4channels as described herein contain TRPM4polypeptides, which are in turn encoded by TRPM4nucleic acids. The ion channels described herein are preferably formed in HEK-293 cells from one or more novel TRPM4polypeptides, which exhibit one or more of the unique TRPM4properties described herein.

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Honolulu, HI, United States of America

Reinhold Penner