Enhancers of induced pluripotent stem cell reprogramming

Patent metadata

Field	Value
Publication number	US-9951316-B2
Application number	US-201514591341-A
Country	US
Kind code	B2
Filing date	Jan 7, 2015
Priority date	Dec 3, 2012
Publication date	Apr 24, 2018
Grant date	Apr 24, 2018

Abstract

Described herein, inter alia, are methods and compositions useful for induced pluripotent stem cell reprogramming.

First claim

What is claimed is:

1. An in vitro method of expressing an Oct4 protein in a cell, the method comprising
(i) contacting a non-pluripotent cell with a compound having the formula:

wherein,
X 1 is C(R 12 ) or N;
X 2 is C(R 4 ) or N;
X 3 is C(R 5 ) or N;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are independently selected from hydrogen, halogen, —CN, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , —OH, —SH, —SO 3 H, —C(O)OH, —C(O)NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, wherein R 2 and R 3 are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
(ii) after step (i), culturing-said non-pluripotent cell for a sufficient amount of time for said non-pluripotent cell to express an Oct4 protein; and
wherein the compound is not:

2. The method of claim 1 , wherein the compound is selected from the group consisting of

3. The method of claim 1 , wherein the compound is selected from the group consisting of

4. The method of claim 1 , wherein the compound is selected from the group consisting of

5. The method of claim 1 , wherein R 2 and R 3 are joined together to form a substituted or unsubstituted heteroaryl.

6. The method of claim 1 , wherein R 2 and R 3 are joined together to form a substituted or unsubstituted five-membered heteroaryl.

7. The method of claim 1 ,
wherein,
X 1 is C(H) or N;
X 2 is C(H);
X 3 is C(R 5 ) or N;
R 2 and R 6 are independently selected from hydrogen, halogen, —CN, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , —OH, —SH, —SO 3 H, —C(O)OH, —C(O)NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 3 is independently selected from hydrogen, halogen, —CN, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , —OH, —SH, —SO 3 H, —C(O)OH, —C(O)NH 2 , unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, wherein R 2 and R 3 are optionally joined to form a substituted or unsubstituted heteroaryl;
R 7 is hydrogen;
R 1 , R 5 , R 8 , R 9 , R 10 , and R 11 are independently selected from hydrogen, halogen, —CN, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , —OH, —SH, —SO 3 H, —C(O)OH, —C(O)NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

8. The method of claim 1 ,
wherein,
X 1 is C(H) or N;
X 2 is C(H);
X 3 is C(R 5 ) or N;
R 1 is hydrogen, halogen, —CF 3 , —CCl 3 , unsubstituted alkyl, or unsubstituted heteroalkyl;
R 2 and R 6 are independently hydrogen, halogen, —CF 3 , —CCl 3 , or unsubstituted alkyl;
R 3 is independently hydrogen, halogen, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , unsubstituted alkyl, substituted or unsubstituted heteroalkyl, wherein R 2 and R 3 are optionally joined to form an unsubstituted 5 membered heteroaryl;
R 5 is hydrogen or unsubstituted alkyl;
R 7 , R 8 , R 9 , R 10 , and R 11 are hydrogen.

9. The method of claim 1 ,
wherein,
X 1 is C(H) or N;
X 2 is C(H);
X 3 is C(R 5 ) or N;
R 1 is hydrogen, halogen, unsubstituted methoxy, or unsubstituted ethoxy;
R 2 is independently hydrogen, halogen, —CF 3 , or unsubstituted methyl;
R 3 is independently hydrogen, halogen, —NO 2 , —NH 2 , —N(CH 3 ) 2 , unsubstituted C 1 -C 3 alkyl, unsubstituted methoxy, unsubstituted ethoxy, wherein R 2 and R 3 are optionally joined to form an unsubstituted oxadiazolyl;
R 5 is hydrogen or unsubstituted methyl;
R 6 is independently hydrogen, halogen, —CF 3 , or unsubstituted C 1 to C 5 alkyl; and
R 7 , R 8 , R 9 , R 10 , and R 11 are hydrogen.

10. The method of claim 1 , wherein the compound is selected from the group consisting of

11. The method of claim 7 ,
wherein,
R 6 is independently selected from halogen, —CN, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , —OH, —SH, —SO 3 H, —C(O)OH, —C(O)NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; and
R 3 is independently selected from hydrogen, halogen, —CN, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , —OH, —SH, —SO 3 H, —C(O)OH, —C(O)NH 2 , unsubstituted alkyl, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, wherein R 2 and R 3 are optionally joined to form a substituted or unsubstituted heteroaryl.

12. The method of claim 8 ,
wherein,
R 6 is independently halogen, —CF 3 , —CCl 3 , or unsubstituted alkyl; and
R 3 is independently hydrogen, halogen, —NO 2 , —NH 2 , —CF 3 , —CCl 3 , unsubstituted alkyl, unsubstituted heteroalkyl, wherein R 2 and R 3 are optionally joined to form an unsubstituted 5 membered heteroaryl.

Assignees

• Hope City

Inventors

• Shi Yanhong
• Yip Man Lun
• Li Wendong

Classifications

• C12N5/0696 Primary

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

• C12N2501/603

  Oct-3/4 · CPC title

• C12N2506/1307

  from adult fibroblasts · CPC title

• C12N2506/02

  from embryonic cells · CPC title