Polycomb repressive complex 2 (PRC2) inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-9388213-B2
Application number	US-201314023223-A
Country	US
Kind code	B2
Filing date	Sep 10, 2013
Priority date	Sep 10, 2012
Publication date	Jul 12, 2016
Grant date	Jul 12, 2016

Abstract

The present invention relates to Polycomb Repressive Complex 2 (PRC2) peptide inhibitors and their use for the treatment of cancer and other conditions associated with aberrant PRC2 methyltransferase activity.

First claim

What is claimed is:

1. An isolated peptide comprising an amino acid sequence of XAARMSXPXXG (SEQ ID NO:4), wherein X is any amino acid residue, wherein said peptide is between 10-50 amino acids in length, and wherein the peptide is acetylated at the N-terminus and amidated at the carboxy terminus.

2. The isolated peptide of claim 1 , wherein X at position 1 is a lysine or arginine residue, X at position 7 is an alanine or serine residue, and X at position 9 and position 10 is a serine, alanine, or threonine residue.

3. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of TXAARMSXPXXGGVK (SEQ ID NO: 41).

4. The isolated peptide of claim 1 , wherein said peptide comprises the amino acid sequence of KQLATXAARMSXPXXGGVKK (SEQ ID NO: 44).

5. A fusion peptide comprising:
an isolated peptide that is between 10-50 amino acids in length and comprises an amino acid sequence of XAARMSXPXXG (SEQ ID NO:4), wherein X is any amino acid residue;
and one or more targeting moieties coupled to the isolated peptide.

6. The fusion peptide of claim 5 , wherein the targeting moiety is a cell specific targeting moiety.

7. The fusion peptide of claim 5 , wherein the targeting moiety is a cell uptake moiety.

8. The fusion peptide of claim 7 , wherein the cell uptake moiety comprises a trans-activator of transcription (TAT) protein or peptide thereof.

9. The fusion peptide of claim 5 , wherein the targeting moiety is a nuclear localization moiety.

10. A pharmaceutical composition comprising:
the isolated peptide of claim 1 and
a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 further comprising:
a delivery vehicle.

12. A method of treating a subject having cancer comprising:
selecting a subject having cancer, wherein said cancer is selected from the group consisting of leukemia, lymphoma, breast cancer, melanoma, bladder cancer, gastric cancer, endometrial cancer, prostate cancer, Ewing sarcoma, and non-small cell lung cancer; and administering the isolated peptide of claim 1 to the subject under conditions effective to treat the cancer.

13. The method of claim 12 , wherein said cancer is mediated by increased PRC2 activity.

14. The method of claim 12 , wherein X at position 1 of SEQ ID NO: 4 is a lysine or arginine residue, X at position 7 is an alanine or serine residue, and X at position 9 and position 10 is a serine, alanine, or threonine residue.

15. The method of claim 12 , wherein said peptide comprises the amino acid sequence of TXAARMSXPXXGGVK (SEQ ID NO: 41).

16. The method of claim 12 , wherein said peptide comprises the amino acid sequence of KQLATXAARMSXPXXGGVKK (SEQ ID NO: 44).

17. A method of treating a subject having cancer comprising:
selecting a subject having cancer, wherein said cancer is selected from the group consisting of leukemia, lymphoma, breast cancer, melanoma, bladder cancer, gastric cancer, endometrial cancer, prostate cancer, Ewing sarcoma, and non-small cell lung cancer; and administering the fusion peptide of claim 5 to the subject under conditions effective to treat the cancer.

Assignees

• Univ Rockefeller

Inventors

• Allis C David
• Lewis Peter

Classifications

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K47/48246

  Human Necessities · mapped topic