# US 2013/0280205 A1 · Activators of SGK-1 for Use as Cardioprotective Agents

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- Number: US 2013/0280205 A1
- Document ID: US20130280205A1
- Status: Published application
- Kind: A1
- Application number: 13/740,889
- Filed: 2013-01-14
- Published: 2013-10-24
- Earliest claimed: 2012-01-13
- Assignees: Georgia Regents University
- Applicants: Georgia Regents University
- Inventors: Mahmood Mozaffari; Babak Baban
- Web page: https://patentgrep.com/patent/US20130280205A1

## CPC

- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 31/22: of acyclic acids, e.g. pravastatin
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 38/1758: {p53}
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/1858: {Platelet-derived growth factor [PDGF]}
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/24: Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
- A61K 38/28: Insulins
- A61K 38/30: Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 {(insulin-like growth factor binding protein A61K38/1754)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Q 1/485: {involving kinase}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 2333/9121: with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Compositions for activating SGK-1 are provided. SGK-1 activators can be identified by the methods of screening provided herein. The SGK-1 activators can be used in the disclosed methods of reducing cell death and methods of treating ischemic-reperfusion injury. The ischemic-reperfusion injury can be due to a variety of complications resulting in blood loss to tissue and then the re-establishment of blood flow to the tissue.

## Claims

### Claim 1

A method for reducing or inhibiting ischemic or ischemic-reperfusion injury in a subject comprising administering to the subject an effective amount of an SGK-1 activator to increase the levels of phosphorylated SGK-1 in endothelial or cardiac tissue of the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the SGK-1 activator is selected from the group consisting of mineralocorticoids, gonadotropins, 1,25(OH)2D3, p53, cell-volume and hypotonic, cytokines such as GM-CSF and TNF-alpha, TGF-beta, serum, insulin, IGF-1, fibroblast- and platelet-derived growth factor, activators of the Erk signaling cascade, 12-O-tetradecanoylphorbol-13-acetate (TPA), and combinations thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the ischemic or ischemic-reperfusion injury is due to primary reperfusion therapy.

### Claim 4 (depends on 1)

The method of claim 1, wherein the ischemic or ischemic-reperfusion injury results from myocardial infarction.

### Claim 5

A method for screening for activators of SGK-1 comprising determining the ability of a test compound to modulate the expression, phosphorylation or activity of SGK-1.

### Claim 6 (depends on 5)

The method of claim 5 further comprising
a) contacting the test compound to SGK-1; and
b) measuring the expression, phosphorylation or activity of SGK-1, wherein a compound that increases expression, phosphorylation or activity of SGK-1 is identified as an SGK-1 activator.

### Claim 7

A method of reducing cell death comprising contacting an injured or diseased tissue with a therapeutically effective amount of an SGK-1 activator.

### Claim 8 (depends on 7)

The method of claim 7, wherein the cell death is reduced in the presence of an SGK-1 activator compared to in the absence of an SGK-1 activator.

### Claim 9 (depends on 7)

The method of claim 7, wherein the cell is a cardiomyocyte.

### Claim 10 (depends on 7)

The method of claim 7, wherein the tissue has ischemic-reperfusion injury.

### Claim 11

A method of preventing or treating an ischemic-reperfusion injury comprising administering to a subject a composition comprising a therapeutically effective amount of an SGK-1 activator following myocardial infarction or primary reperfusion therapy.

### Claim 12 (depends on 11)

The method of claim 11, wherein the composition further comprises a pharmaceutically acceptable excipient.

### Claim 13 (depends on 11)

The method of claim 11, wherein the subject has suffered a myocardial infarction.

### Claim 14

A pharmaceutical composition comprising a therapeutically effective amount of an SGK-1 activator to increase levels of phosphorylated SGK-1 in endothelial or cardiac tissue of a subject and a pharmaceutically acceptable excipient.