Agents and methods for treating CBP-dependent cancers

Patent metadata

Field	Value
Publication number	US-11208446-B2
Application number	US-201716346834-A
Country	US
Kind code	B2
Filing date	Nov 1, 2017
Priority date	Nov 1, 2016
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

Abstract

Single chain peptides comprising either a cell penetrating HIV-TAT peptide sequence and a MYB:CBP complex interfering peptide sequence from MYB, or comprising a cell penetrating HIV-TAT peptide sequence, a CBP binding peptide sequence from CREB and a MYB:CBP complex interfering peptide sequence from MYB, are provided for use in preventing MYB:CBP complex formation and downstream events leading to cancer, in particular a leukemia. Both L-amino acid single chain peptides and retro-inverso single chain peptides are provided.

First claim

What is claimed is:

1. A single chain peptide consisting of D-amino acids and comprising: an N-terminal portion comprising the amino acid sequence selected from KLENETSMLLLELEKIRK (SEQ ID NO:19) and KLENETSMLLLEL (SEQ ID NO:24); a C-terminal portion comprising the amino acid sequence RRRQRRKKRGY (SEQ ID NO:17); and the amino acid sequence therebetween selected from PADSSLDNLIKRYpSPRRSLIERR (SEQ ID NO:33), KRYpSPRRSLIERR (SEQ ID NO:23) and PADSSLDNLIKRYpS (SEQ ID NO:34).

2. The single chain peptide of claim 1 , wherein a linker is present between the amino acid sequences thereof.

3. The single chain peptide of claim 2 , wherein the linker is GG.

4. The single chain peptide of claim 1 , wherein the single chain peptide consists of the D-amino acid sequence KLENETSMLLLELKRYpSPRRSLIERRGGRRRQRRKKRGY (SEQ ID NO:25).

5. The single chain peptide of claim 4 , wherein the N-terminus is acetylated, the C-terminus is amidated, or the combination thereof.

6. The single chain peptide of claim 1 , wherein the N-terminus is acetylated, the C-terminus is amidated, or the combination thereof.

7. The single chain peptide of claim 1 , wherein the single chain peptide comprises the D-amino acid sequence KLENETSMLLLELKRYpSPRRSLIERRGGRRRQRRKKRGY (SEQ ID NO:25).

8. The single chain peptide of claim 7 , wherein the N-terminus is acetylated, the C-terminus is amidated, or the combination thereof.

9. A method for treating acute myeloid leukemia comprising administering to a patient in need thereof an effective amount of a composition comprising a peptide of claim 1 , and a carrier, excipient or diluent.

Assignees

• Memorial Sloan Kettering Cancer Center
• Memorial Sloan Kettering Cancer Cenier

Inventors

• Kentsis Alex
• Ramaswamy Kavitha
• Marek Lauren

Classifications

• C07K14/4705 Primary

  stimulating, promoting or activating activity · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title