Specific Akt3 inhibitor and uses thereof

Patent metadata

Field	Value
Publication number	US-10292978-B2
Application number	US-201715407659-A
Country	US
Kind code	B2
Filing date	Jan 17, 2017
Priority date	Jan 15, 2016
Publication date	May 21, 2019
Grant date	May 21, 2019

Abstract

Methods of selectively inhibiting Akt3 are provided. It has been discovered that 4-[(6-nitroquinolin-4-yl)amino]-N-[4-(pyridin-4-ylamino)phenyl]benzamide selectively inhibits Akt3. Because Akt3 modulates the suppressive function of natural Tregs and the polarization of induced Tregs, 4-[(6-nitroquinolin-4-yl)amino]-N-[4-(pyridin-4-ylamino)phenyl]benzamide can be used for modulating immune responses.

First claim

We claim:

1. A method of decreasing an immune suppressive response in a subject in need thereof comprising administering to the subject a composition comprising 0.01 to 50 mg/kg of 4-[(6-nitroquinolin-4-yl)amino]-N-[4-(pyridin-4-ylamino)phenyl]benzamide that selectively inhibits Akt3 by an amount effective to reduce the immune suppressive function of Tregs in the subject.

2. The method of claim 1 wherein the subject has cancer or an infection.

3. The method of claim 2 , 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.

4. The method of claim 2 , wherein the infectious disease is caused by bacterium, virus, protozoan, helminth, or other microbial pathogen.

5. The method of claim 1 , 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).

6. The method of claim 5 wherein the immune suppressive function of nTreg is the secretion of one or more anti-inflammatory cytokines.

7. The method of claim 6 wherein the anti-inflammatory cytokine is IL10, TGFβ, or a combination thereof.

8. The method of claim 1 , further comprising administering to the subject a second active agent that is selected from the group consisting of chemotherapeutic agents, cytokines, chemokines, and radiation therapy.

9. The method of claim 1 , further comprising administering to the subject a second Akt3 inhibitor that is a compound selected from the group consisting of

Assignees

• Univ Res Inst Inc Augusta

Inventors

• Khleif Samir N
• Mkrtichyan Mikayel
• Lebedyeva Iryna

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title