# US 11,026,952 B2 · Small molecules for mouse satellite cell proliferation

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- Number: US 11,026,952 B2
- Document ID: US11026952B2
- Status: Granted
- Kind: B2
- Application number: 16/074,766
- Filed: 2017-02-01
- Published: 2019-12-05
- Granted: 2021-06-08
- Earliest claimed: 2011-06-16
- Assignees: President and Fellows of Harvard College
- Applicants: President and Fellows of Harvard College
- Inventors: Lee L. Rubin; Amy J. Wagers; Amanda K. W. Gee; Feodor D. Price
- Web page: https://patentgrep.com/patent/US11026952B2

## CPC

- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61K 31/403: condensed with carbocyclic rings, e.g. carbazole
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- 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

## Abstract

The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided are methods for repairing or regenerating a damaged muscle tissue of a subject.

## Claims

### Claim 1

A method of increasing satellite cell proliferation, the method comprising: contacting a satellite cell with a p38 MAPK inhibitor selected from the group consisting of SB 239063 (trans-1-(4-Hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyridimidin-4-yl)imidazole; HMSL10036-101-1); Doramapimod (BIRB 796; HMSL10169-101-1); SB 203580 (RWJ 64809; PB 203580; HMSL10167-101-1); Neflamapimod (VX-745; HMSL10168-101-1); PH-797804 (HMSL10439-101); VX-702 (HMSL10440-101); SB202190 (HMSL10441-101); Ralimetinib (LY2228820; HMSL10438-103); Losmapimod (GSK-AHAB; SB856553; GW856553X; HMSL10402-101); and any combinations thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the p38 MAPK inhibitor is contacted with the satellite cell at a concentration of about 0.01 nM to about 100 μM.

### Claim 3 (depends on 1)

The method of claim 1, wherein said contacting is for at least 1 hour.

### Claim 4 (depends on 1)

The method of claim 1, wherein said contacting is for one to seven days.

### Claim 5 (depends on 1)

The method of claim 1, wherein the contact is in vitro.

### Claim 6 (depends on 1)

The method of claim 1, wherein the contact is ex vivo.

### Claim 7 (depends on 1)

The method of claim 1, wherein the contact is in vivo.

### Claim 8 (depends on 7)

The method of claim 7, wherein in vivo contact is in a mammal.

### Claim 9 (depends on 8)

The method of claim 8, wherein in vivo contact is in a human.

### Claim 10 (depends on 1)

The method of claim 1, wherein the in vivo contact is in a subject, where the subject is in need of treatment for damaged muscle tissue.

### Claim 11 (depends on 10)

The method of claim 10, wherein the damaged muscle tissue is the result of a physical injury or accident, disease, infection, over-use, loss of blood circulation, or muscle atrophy or wasting.

### Claim 12 (depends on 10)

The method of claim 10, wherein the damaged muscle tissue is dystrophic muscle or an ageing muscle.

### Claim 13 (depends on 10)

The method of claim 10, wherein the damaged muscle tissue is the result of muscle atrophy/wasting.

### Claim 14

A method for muscle repair or regeneration in a subject, the method comprising administering a therapeutically effective amount of a p38 MAPK inhibitor selected from the group consisting of SB 239063 (trans-1-(4-Hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyridimidin-4-yl)imidazole; HMSL10036-101-1); Doramapimod (BIRB 796; HMSL10169-101-1); SB 203580 (RWJ 64809; PB 203580; HMSL10167-101-1); Neflamapimod (VX-745; HMSL10168-101-1); PH-797804 (HMSL10439-101); VX-702 (HMSL10440-101); SB202190 (HMSL10441-101); Ralimetinib (LY2228820; HMSL10438-103); Losmapimod (GSK-AHAB; SB856553; GW856553X; HMSL10402-101); and any combinations thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the damaged muscle tissue is the result of a physical injury or accident, disease, infection, over-use, loss of blood circulation, or muscle atrophy or wasting.

### Claim 16 (depends on 14)

The method of claim 14, wherein the damaged muscle tissue is dystrophic muscle or an ageing muscle.