Rhogef12 is a therapeutic target for the treatment of heart failure
OwnerMikito Takefuji, Nina Wettschureck +1inventors
InventorsMikito Takefuji, Nina Wettschureck, Stefan Offermanns
Life of this patent
Estimating the term…
Abstract
The present invention relates to an inhibitor of the Rho guanine nucleotide exchange factor 12 (RhoGEF12) or an inhibitor of an activator of RhoGEF12 for use in the prevention and/or treatment of heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith. Further, it relates also a method of treatment and methods for identifying inhibitors of Rho guanine nucleotide exchange factor 12 (RhoGEF12) or inhibitors of an activator of RhoGEF12.
Claims14
(canceled)
A method of preventing and/or treating heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith comprising administering a pharmaceutically effective amount of an inhibitor of Rho guanine nucleotide exchange factor 12 (RhoGEF12) or an inhibitor of an activator of RhoGEF12 to a subject in need thereof.
A method of identifying an inhibitor of Rho guanine nucleotide exchange factor 12 (RhoGEF12) or an inhibitor of an activator of RhoGEF12 suitable as a lead compound and/or as a medicament for the prevention and/or treatment of heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith, comprising the steps of:
- (a) determining the level of RhoGEF12 protein, the level of RhoGEF12 transcript and/or the level of activity of RhoGEF12 in a cell;
- (b) contacting said cell or a cell of the same cell population with a test compound;
- (c) determining the level of RhoGEF12 protein, the level of RhoGEF12 transcript and/or the level of activity of RhoGEF12 in said cell after contacting with the test compound;
- and
- (d) comparing the level of RhoGEF12 protein, the level of RhoGEF12 transcript and/or the level of activity of RhoGEF12 determined in step (c) with the RhoGEF12 protein, the RhoGEF12 transcript and/or the RhoGEF12 activity level determined in step (a), wherein a decrease of the RhoGEF12 protein, the RhoGEF12 transcript and/or the RhoGEF12 activity level in step (c) as compared to step (a) indicates that the test compound is an inhibitor of RhoGEF12 or an inhibitor of an activator of RhoGEF12 suitable as a lead compound and/or as a medicament for the prevention and/or treatment of heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith.
A method of identifying an inhibitor of Rho guanine nucleotide exchange factor 12 (RhoGEF12) or an inhibitor of an activator of RhoGEF12 suitable as a lead compound and/or as a medicament for the prevention and/or treatment of heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith, comprising the steps of:
- (a) determining the level of activity of an RhoGEF12 target molecule in a cell containing RhoGEF12;
- (b) contacting said cell or a cell of the same cell population with a test compound;
- (c) determining the level of activity of the RhoGEF12 target molecule in said cell after contacting with the test compound;
- and
- (d) comparing the level of activity of the RhoGEF12 target molecule determined in step (c) with the level of activity of the RhoGEF12 target molecule determined in step (a), wherein a decreased activity of the target molecule in step (c) as compared to step (a) indicates that the test compound is an inhibitor of RhoGEF12 or an inhibitor of an activator of RhoGEF12 suitable as a lead compound and/or as a medicament for the prevention and/or treatment of heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith.
A method of preventing or reducing hypertrophy and/or fibrosis of cardiomyocytes comprising:
- contacting said cardiomyocytes with an effective amount of an inhibitor of the Rho guanine nucleotide exchange factor 12 (RhoGEF12) or an inhibitor of an activator of RhoGEF12.
(canceled)
Dependencies are inferred from the claim text.