Small molecule screening for mouse satellite cell proliferation

Patent metadata

Field	Value
Publication number	US-2018153902-A1
Application number	US-201715728476-A
Country	US
Kind code	A1
Filing date	Oct 9, 2017
Priority date	Jun 16, 2011
Publication date	Jun 7, 2018
Grant date	—

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.

First claim

1 . A method of increasing satellite cell proliferation, the method comprising: contacting a satellite cell with a compound comprising a histone deacetylases (HDAC) inhibitor.

2 . The method of claim 1 , wherein the compound is a selective HDAC inhibitor.

3 . The method of claim 1 , wherein the compound is a Class I, Class II, and/or a Class III HDAC inhibitor.

4 . The method of claim 1 , wherein the compound is a short-chain fatty acid, a cyclic tetrapeptide, a compound having a hydroxyamic acid group, a hydroxyamic acid, a cyclic tetrapeptide, a benzamide, a depudecin, a sulfonamide anilide, a compound comprising a cyclic tetrapeptide group and a hydroxamic acid group, a compound comprising a benzamide group and a hydroxamic acid group, an antisense oligonucleotide or ribozyme that inhibits transcription and/or translation of one or more HDACs, or a low molecular weight carboxylate.

5 . The method of claim 1 , wherein the compound is a hydroxyamic acid selected from the group consisting of suberoylanilide hydroxamic acid (SAHA), trichostatin A (TSA), trichostatin C (TSC), salicylhydroxamic acid, oxamflatin, suberic bishydroxamic acid (SBHA), m-carboxycinnamic acid bishydroxamic acid (CBHA), pyroxamide (CAS RN 382180-17-8), diethyl bis-(pentamethylene-N,Ndimethylcarboxamide)malonate (EMBA), azelaic bishydroxamic acid (ABHA), azelaic-1-hydroxamate-9-anilide (AAHA), 6-(3-Chlorophenylureido) carpoic hydroxamic acid, and A-161906.

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

7 . The method of claim 6 , wherein the in vivo contacting is in a human.

8 . The method of claim 6 , wherein the in vivo contacting is in a subject, wherein the subject is in need of treatment for damaged muscle tissue.

9 . The method of claim 8 , 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.

10 . The method of claim 8 , wherein the damaged muscle tissue is the result of muscle atrophy/wasting.

11 . A method for muscle repair or regeneration in a subject, the method comprising administering a therapeutically effective amount of a compound to the subject, wherein the subject has a damaged muscle tissue, and wherein the compound comprises a HDAC inhibitor.

12 . The method of claim 11 , wherein the compound is a selective HDAC inhibitor.

13 . The method of claim 11 , wherein the compound is a Class I, Class II, and/or a Class III HDAC inhibitor.

14 . The method of claim 11 , wherein the compound is a short-chain fatty acid, a cyclic tetrapeptide, a compound having a hydroxyamic acid group, a hydroxyamic acid, a cyclic tetrapeptide, a benzamide, a depudecin, a sulfonamide anilide, a compound comprising a cyclic tetrapeptide group and a hydroxamic acid group, a compound comprising a benzamide group and a hydroxamic acid group, an antisense oligonucleotide or ribozyme that inhibits transcription and/or translation of one or more HDACs, or a low molecular weight carboxylate.

15 . The method of claim 11 , wherein the compound is a hydroxyamic acid and is selected from the group consisting of suberoylanlide hydroxamic acid (SAHA), trichostatin A (TSA), trichostatin C (TSC), salicylhydroxamic acid, oxamflatin, suberic bishydroxamic acid (SBHA), m-carboxycinnamic acid bishydroxamic acid (CBHA), pyroxamide (CAS RN 382180-17-8), diethyl bis-(pentamethylene-N,Ndimethylcarboxamide)malonate (EMBA), azelaic bishydroxamic acid (ABHA), azelaic-1-hydroxamate-9-anilide (AAHA), 6-(3-Chlorophenylureido) carpoic hydroxamic acid, and A-161906.

16 . The method of claim 11 , wherein the subject is human.

17 . The method of claim 11 , 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.

18 . The method of claim 17 , wherein the damaged muscle tissue is the result of muscle atrophy/wasting.

Assignees

• Harvard College

Inventors

• Rubin Lee L
• Gee Amanda
• Wagers Amy J

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61P21/06

  Anabolic agents (androgens A61P5/26) · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/4164

  1,3-Diazoles · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title