Inhibitors of prototypic galectin dimerization and uses thereof

Patent metadata

Field	Value
Publication number	US-10519239-B2
Application number	US-201615576609-A
Country	US
Kind code	B2
Filing date	May 25, 2016
Priority date	May 28, 2015
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

Agents that inhibit the dimerization of a prototypic galectin such as galectin-7 are described. These agents, for example antibodies and peptides, bind to a domain corresponding to residues 13-25, 86-108 and/or 129-135 of human galectin-7. The use of such agents to inhibit a biological, physiological and/or pathological process that involves prototypic galectin dimerization, for example for the inhibition of galectin-7-mediated apoptosis and the treatment of galectin-7-expressing cancers, is also described.

First claim

What is claimed is:

1. A peptide which is of one of the following sequences: Leu-Asp-Ser-Val-Arg-Ile-Phe-NH 2 (SEQ ID NO:2), Ile-Arg-Pro-Gly-Thr-Val-Leu-Arg-Gly-Leu-Val-NH 2 (SEQ ID NO:4), Asp-Gly-Phe-Lys-Ala-Val-Val-Gly-Asp-Ala-Gln-Tyr-His-His-NH 2 (SEQ ID NO:6) or Phe-Glu-Val-Leu-Ile-Ile-Ala-Ser-Asp-Asp-Gly-Phe-Lys-Ala-Val-Val-Gly-NH 2 (SEQ ID NO:8), or a salt thereof.

2. The peptide or salt thereof of claim 1 , which is: Leu-Asp-Ser-Val-Arg-Ile-Phe-NH 2 (SEQ ID NO:2).

3. The peptide or salt thereof of claim 1 , which Ile-Arg-Pro-Gly-Thr-Val-Arg-Ile-Arg-Gly-Leu-Val-NH 2 (SEQ ID NO:4).

4. The peptide or salt thereof of claim 1 , which is: Asp-Gly-Phe-Lys-Ala-Val-Val-Gly-Asp-Ala-Gln-Tyr-His-His-NH 2 (SEQ NO:6).

5. The peptide or salt thereof of claim 1 , which is: Phe-Glu-Val-Leu-Ile-Ile-Ala-Ser-Asp-Asp-Gly-Phe-Lys-Ala-Vasl-Val-Gly-NH 2 (SEQ ID NO:8).

6. A method for inhibiting the dimerization of native human galectin-7, said method comprising contacting said native human, galectin-7 with an effective amount of the peptide or salt thereof defined in claim 1 .

7. The method of claim 6 , wherein the peptide or salt thereof is: Leu-Asp-Ser-Val-Arg-Ile-Phe-NH 2 (SEQ ID NO:2).

8. A method for inhibiting galectin-7-mediated apoptosis in, a cell, said method comprising contacting said cell with an effective amount of the peptide or salt thereof defined in claim 1 .

9. The method of claim 8 , wherein the peptide or salt thereof is: Leu-Asp-Ser-Val-Arg-Ile-Phe-NH 2 (SEQ ID NO:2).

10. A method for treating a galectin-7-expressing-cancer in a subject, said method comprising administering to said subject an effective amount of the peptide or salt thereof defined in claim 1 .

11. The method of claim 10 , wherein the peptide or salt thereof is: Leu-Asp-Ser-Val-Arg-Ile-Phe-NH 2 (SEQ ID NO:2).

12. The method of claim 10 , wherein said galectin-7-expressing cancer is a breast cancer, an ovarian cancer, or a lymphoma.

13. The method of claim 12 , wherein the peptide or salt thereof is: Leu-Asp-Ser-Val-Arg-Ile-Phe-NH 2 (SEQ ID NO:2).

14. The method of claim 12 , wherein the galectin-7-expressing cancer is breast cancer.

15. The method of claim 12 , wherein the galectin-7-expressing cancer is ovarian cancer.

16. The method of claim 12 , wherein the galectin-7-expressing cancer is lymphoma.

17. The method of claim 13 , wherein the galectin-7-expressing cancer is breast cancer.

18. The method of claim 13 , wherein the galectin-7-expressing cancer is ovarian cancer.

19. The method of claim 13 , wherein the galectin-7-expressing cancer is lymphoma.

Assignees

• Inst Nat Rech Scient

Inventors

• Chatenet David
• Doucet Nicolas
• St-Pierre Yves
• Vladoiu Maria-Claudia

Classifications

• 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

• C07K14/4702

  Regulators; Modulating activity · CPC title

• A61K38/08

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K16/2851 Primary

  against the lectin superfamily, e.g. CD23, CD72 · CPC title

• G01N2500/04

  Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A) · CPC title