# US 2019/0167787 A1 · Methods and Compositions for Inhibiting Akt3

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- Number: US 2019/0167787 A1
- Document ID: US20190167787A1
- Status: Published application
- Kind: A1
- Application number: 16/269,146
- Filed: 2019-02-06
- Published: 2019-06-06
- Earliest claimed: 2016-01-15
- Assignees: Augusta University Research Institute, Inc.
- Applicants: Augusta University Research Institute, Inc.
- Inventors: Samir N. Khleif; Mikayel Mkrtichyan
- Web page: https://patentgrep.com/patent/US20190167787A1

## CPC

- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/0011: {Cancer antigens}
- A61P 35/00: Antineoplastic agents
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- A61K 2039/55511: {Organic adjuvants}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds and compositions for selectively inhibiting Akt3 are provided. Methods of using the compounds are also provided. Because Akt3 modulates the suppressive function of natural Tregs and the polarization of induced Tregs, the disclosed compounds are useful for modulating immune responses.

## Claims

### Claim 1

A compound selected from the group consisting of
or an enantiomer, polymorph, or pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising one or more of the compounds of claim 1.

### Claim 3 (depends on 1)

A method of decreasing an immune suppressive response in a subject in need thereof comprising administering to the subject a composition comprising one or more compounds according to claim 1 that selectively inhibits Akt3 by an amount effective to reduce the immune suppressive response in the subject.

### Claim 4 (depends on 3)

The method of claim 3 wherein the subject has cancer or an infection.

### Claim 5 (depends on 1)

A method of treating cancer comprising administering to a subject with cancer a composition comprising one or more compounds according to claim 1 that selectively inhibits Akt3 in an amount effective to reduce an immune suppressive response in the subject.

### Claim 6 (depends on 4, 5)

The method of any one of claim 4 or 5 wherein the cancer is selected from the group consisting of bladder, brain, breast, cervical, colo-rectal, esophageal, kidney, liver, lung, nasopharangeal, pancreatic, prostate, skin, stomach, uterine, ovarian, testicular and hematologic cancers.

### Claim 7 (depends on 1)

A method of treating an infectious disease comprising administering to a subject with an infectious disease a composition comprising one or more compounds according to claim 1 that selectively inhibits Akt3 in an amount effective to reduce an immune suppressive response in the subject.

### Claim 8 (depends on 4)

The method of any one of claim 4, wherein the infectious disease is caused by bacterium, virus, protozoan, helminth, or other microbial pathogen.

### Claim 9 (depends on 3)

The method of claim 3, wherein the immune suppressive response that is reduced is selected from the group consisting of an immune suppressive function of natural Treg (nTreg) and induction of conventional T cells into induced Treg (iTreg).

### Claim 10 (depends on 9)

The method of claim 9 wherein the immune suppressive function of nTreg is the secretion of one or more anti-inflammatory cytokines.

### Claim 11 (depends on 10)

The method of claim 10 wherein the anti-inflammatory cytokine is IL 10, TGFP, or a combination thereof.

### Claim 12 (depends on 1)

The method of claim 1, further comprising administering to the subject a second active agent.