Compositions and methods for treating tissue injury

Patent metadata

Field	Value
Publication number	US-11931339-B2
Application number	US-201917256066-A
Country	US
Kind code	B2
Filing date	Jun 25, 2019
Priority date	Jun 25, 2018
Publication date	Mar 19, 2024
Grant date	Mar 19, 2024

Abstract

A method for preventing or treating a tissue injury and/or promoting tissue repair in a subject in need thereof, includes administering to the subject a therapeutically effective amount of an ADH inhibitor, AKR inhibitor, SCoR inhibitor, and/or PKM2 inhibitor.

First claim

Having described the invention, I claim:

1. A method for preventing or treating acute kidney injury associated with renal ischemia reperfusion injury in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of an AKR1A1 inhibitor in combination with nicotinamide adenine dinucleotide (NAD + ) and/or a NAD+ precursor, wherein the AKR1A1 inhibitor includes a compound selected from the group consisting of:

 and pharmaceutically acceptable salts thereof.

2. The method of claim 1 , wherein the amount of AKR1A1 inhibitor administered to the subject is an amount effective to induce renal vasodilatation, enhance resistance to hypoxia, improve renal hemodynamics, decrease renal oxidative stress, reduce renal inflammation, and/or preserve renal function.

3. The method of claim 1 , wherein the AKR1A1 inhibitor is administered before and/or after the ischemia reperfusion injury.

4. The method of claim 1 , wherein the AKR1A1 inhibitor is administered at a range of about 1 minute to about 72 hours before the ischemia reperfusion injury.

5. The method of claim 1 , wherein the is administered at at least about 2 hours before the ischemia reperfusion injury.

6. The method of claim 1 , wherein the AKR1A1 inhibitor is administered at least about 30 minutes after the ischemic reperfusion injury.

7. The method of claim 1 , wherein the renal ischemia reperfusion injury is associated with a kidney transplant in the subject.

8. The method of claim 1 , wherein the AKR1A1 inhibitor is administered at an amount(s) effective to promote S-nitrosylation of proteins in the subject.

9. The method of claim 1 , wherein the AKR1A1 inhibitor has a selectivity for AKR1A1 versus AKR1B1≥2 or more times.

10. The method of claim 1 , wherein a selective or partially selective AKR1A1 inhibitor is administered in combination with a selective or partially selective AKR1B1 inhibitor.

11. The method of claim 10 , wherein the AKR1B1 inhibitor has a selectivity for AKR1B1 versus AKR1A1≥2 or more times.

12. The method of claim 1 , wherein the NAD+ precursor is selected from the group consisting of tryptophan, nicotinic acid, nicotinic acid riboside, nicotinamide riboside (NR), and nicotinamide (NAM).

Assignees

• Univ Case Western Reserve
• Univ Hospitals Cleveland Medical Center

Inventors

• Stamler Jonathan S

Classifications

• A61P13/12

  of the kidneys · CPC title

• A61K31/352

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• A61K31/424

  condensed with heterocyclic ring systems, e.g. clavulanic acid · CPC title

• A61K31/422

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/4166 Primary

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title