# US 2026/0224523 A1 · Induction of Proteasomal Activity in Mammalian Cells by Lifespan-extending tRNA Synthetase Inhibitors

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- Number: US 2026/0224523 A1
- Document ID: US20260224523A1
- Status: Published application
- Kind: A1
- Application number: 19/179,017
- Filed: 2025-04-15
- Published: 2026-08-06
- Earliest claimed: 2024-04-23
- Assignees: UNM Rainforest Innovations
- Applicants: Unm Rainforest Innovations
- Inventors: MARK A. McCORMICK; BLAISE L. MARINER
- Web page: https://patentgrep.com/patent/US20260224523A1

## CPC

- A61K 31/365: Lactones
- A61K 31/351: not condensed with another ring
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/549: having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/69: Boron compounds
- A61K 38/1709: {from mammals}
- A61K 38/45: Transferases (2)
- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Y 207/11001: Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
- 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)
- C12Y: ENZYMES

## Abstract

The present invention is directed to methods for treating, delaying, inhibiting, ameliorating or reducing the likelihood of neurodegenerative disease in a patient in need or at risk using tRNA synthetase inhibitors including borrelidin, mupirocin, tavaborole, halofuginone, LysRS-IN-2, REP 3132 (CRS-3132), REP8839 and mixtures thereof, among others as described herein.

## Claims

### Claim 1

A method of treating, inhibiting, ameliorating, delaying the onset of or reducing the likelihood of a neurodegenerative disease in a patient in need or at risk comprising administering at least one tRNA synthetase inhibitor to the patient.

### Claim 2 (depends on 1)

The method according to claim 1 wherein said neurodegenerative disease is a dementia-type diseases, demyelinating disease, a parkinsonism-type disease, a motor neuron disease, a tauopathy or a prion disease.

### Claim 3 (depends on 1, 2)

The method according to claim 1 or 2 wherein said neurodegenerative disease is Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy (CTE), Lewy body dementia, limbic predominant age-related TDP-43 encephalopathy (LATE), multiple sclerosis (MS), multiple system atrophy and neuromyletis optica spectrum disorder (NMOSD), Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), Pick's disease, corticobasal degeneration, Creutzfeldt-Jacob disease (CJD), variant Creutzfeldt-Jacob disease (VCJD), variably protease-sensitive prionopathy (VPSPr), Gerstmann-Sträussler-Scheinker disease (GSS), Kuru or Fatal insomnia (FI).

### Claim 4 (depends on 2)

The method according to claim 2 wherein said neurodegenerative disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS) or multiple sclerosis.

### Claim 5 (depends on 1, 2, 3, 4)

The method according to any one of claims 1-4 wherein said tRNA synthetase inhibitor is borrelidin, mupirocin, tavaborole (AN2690), halofuginone, LysRS-IN-2 (N-[(4,4-difluoro-1-hydroxycyclohexyl)methyl]-6-fluoro-4-oxochromene-2-carboxamide), cladosporin (asperentin), REP3132 (CRS-3132) REP8839, ganfeborole, PT638, PT662, GSK656, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1, 2, 3, 4)

The method according to any one of claims 1-4 wherein said tRNA synthetase inhibitor is borrelidin, mupirocin, tavaborole (AN2690), halofuginone, LysRS-IN-2 (N-[(4,4-difluoro-1-hydroxycyclohexyl)methyl]-6-fluoro-4-oxochromene-2-carboxamide), cladosporin (asperentin), REP3132 (CRS-3132), REP8839, or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The method according to any one of claims 1-6 wherein said tRNA synthetase inhibitor is co-administered with an additional bioactive agent.

### Claim 8 (depends on 7)

The method according to claim 7 wherein said additional bioactive agent is selected from the group consisting of aducanumab, solanezumab, semorinemab, verubecestate, semagacesta (for AD), prasinezumab, affitope PD01a, a mGluR5 antagonist, a mGlur agonist, a mGlur4 agonist, SV2C and LRRK2 or a pharmaceutically acceptable salt thereof.

### Claim 9

A pharmaceutical composition comprising an effective amount of a tRNA synthetase inhibitor and at least one additional bioactive agent.

### Claim 10 (depends on 9)

The composition according to claim 9 wherein said tRNA synthetase inhibitor is borrelidin, mupirocin, tavaborole (AN2690), halofuginone, LysRS-IN-2 (N-[(4,4-difluoro-1-hydroxycyclohexyl)methyl]-6-fluoro-4-oxochromene-2-carboxamide), cladosporin (asperentin), REP3132 (CRS-3132) REP8839, ganfeborole, PT638, PT662, GSK656, or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 9)

The composition according to claim 9 wherein said tRNA synthetase inhibitor is borrelidin, mupirocin, tavaborole (AN2690), halofuginone, LysRS-IN-2 (N-[(4,4-difluoro-1-hydroxycyclohexyl)methyl]-6-fluoro-4-oxochromene-2-carboxamide), cladosporin (asperentin), REP3132 (CRS-3132), REP8839, or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 9, 10, 11)

The composition according to any one of claims 9-11 wherein said additional bioactive agent is selected from the group consisting of aducanumab, solanezumab, semorinemab, verubecestate, semagacesta (for AD), prasinezumab, affitope PD01a, a mGluR5 antagonist, a mGlur agonist, a mGlur4 agonist, SV2C and LRRK2 or a pharmaceutically acceptable salt thereof.