Compositions and methods for inducing cell dedifferentiation

Patent metadata

Field	Value
Publication number	US-9334481-B2
Application number	US-201213594524-A
Country	US
Kind code	B2
Filing date	Aug 24, 2012
Priority date	Nov 10, 2003
Publication date	May 10, 2016
Grant date	May 10, 2016

Abstract

The present invention provides compounds, compositions and methods for dedifferentiating lineage committed mammalian cells into stem cells. The present invention also provides methods of inducing dedifferentiation of lineage committed mammalian cells into stem cells, which can be further differentiated into various lineage committed cells. Methods of identifying additional compounds useful for inducing dedifferentiation of lineage committed cells into stem cells are also provided.

First claim

What is claimed is:

1. A compound of Formula I having the following structure:

wherein:
R 1 is a member selected from the group consisting of

R 2 is a member selected from the group consisting of -L-R 3 ; wherein
L is —NR 4 —, wherein R 4 is H;
R 3 is C 6-8 cycloalkyl substituted with 1-2 R 3a groups that are independently selected from the group consisting of halogen, C 1-4 alkyl, C 1-4 alkoxy, —N(R 3b , R 3b ), —SO 2 N(R 3b , R 3b ), —C(O)N(R 3b , R 3b ) and —O-aryl, or when said R 3a groups are on adjacent ring atoms they are optionally taken together to form a member selected from the group consisting of —O—(CH 2 ) 1-2 —O—, —O—C(CH 3 ) 2 CH 2 — and —(CH 2 ) 3-4 ; and
each R 3b group is a member that is independently selected from the group consisting of hydrogen and C 1-4 alkyl.

2. A compound of Formula I having the following structure:

wherein:
R 1 is a member selected from the group consisting of

and
R 2 is a member selected from the group consisting of:

3. The compound of claim 2 , wherein said compound is a member selected from the group consisting of:

4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition of claim 5 , wherein said compound is a member selected from the group consisting of:

7. A method of inducing dedifferentiation of a lineage committed cell ex vivo, the method comprising:
contacting a lineage committed mammalian cell with a compound of any one of claims 1 , 2 , or 3 , whereby the mammalian cell dedifferentiates into a multipotent stem cell.

8. The method of claim 7 , further comprising detecting dedifferentiation of the mammalian cell into a multipotent stem cell.

9. The method of claim 7 , whereby differentiation of the lineage committed mammalian cell into a multipotent stem cell is detected by detecting loss of expression of a marker gene expressed by the lineage committed mammalian cell.

10. The method of claim 9 , wherein said lineage committed cell is a myoblast cell.

11. The method of claim 10 , wherein the marker gene is a member selected from the group consisting of: MyoD, Myf5, myosin, CD56 and desmin.

12. The method of claim 10 , wherein the myoblast cell is isolated from a mouse.

13. The method of claim 10 , wherein the myoblast cell is isolated from a primate.

14. The method of claim 13 , wherein the primate is a human.

Assignees

• Chen Shuibing
• Ding Sheng
• Schultz Peter G
• Scripps Research Inst

Inventors

• Chen Shuibing
• Ding Sheng
• Schultz Peter G

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D473/24

  one nitrogen and one sulfur atom · CPC title

• C12N5/0696 Primary

  Artificially induced pluripotent stem cells, e.g. iPS · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P19/10

  for osteoporosis · CPC title