USE OF A COMPOUND FOR ENHANCING THE EXPRESSION OF MEMBRANE PROTEINS ON THE CELL SURFACE

• US 20090017006A1
• Filed: 07/03/2006
• Published: 01/15/2009
• Est. Priority Date: 07/06/2005
• Status: Abandoned Application

• Current Assignee: Axentis Pharma AG
• Original Assignee: Biodevelops Pharma Entwicklung GmbH
• Inventors: Korkhov, Volodymyr M., Milojevic, Tetyana, Nanoff, Christian, Freissmuth, Michael
• Application Number:
  US11/994,947
• Publication Number:
  US 20090017006A1
• Time in Patent Office: Days
• US Class Current: 424/94.630
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

The present invention is directed to the use of Bortezomib and/or a pharmaceutically acceptable salt or ester thereof for the manufacture of a medicament for enhancing the expression of membrane proteins on the cell surface. Especially, the invention is directed to the use of Bortezomib for the manufacture of a medicament for the treatment of a disease of condition selected from the group consisting of cystic fibrosis, diabetes insipidus, hypercholesterinaemia and long QT-syndrome-2.

Claims

1. The use of Bortezomib and/or a pharmaceutically acceptable salt or ester thereof for the manufacture of a medicament for enhancing the expression of membrane proteins on the cell surface.

2. The use according to claim 1, characterized in that the medicament additionally comprises a compound stimulating deubiquitinating activity in a cell.

3. The use according to claim 2, characterized in that said additional compound is selected from the group consisting of

a deubiquitinating enzyme and

a nucleic acid sequence encoding a deubiquitinating enzyme.

4. The use according to claim 3, characterized in that the deubiquitinating enzyme is selected from the group consisting of ubiquitin carboxy-terminal hydrolases (UCH) and ubiquitin specific proteases (USP).

5. The use according to claim 4, characterized in that the deubiquitinating enzyme is USP-4.

6. The use according to any one of the foregoing claims for the manufacture of a medicament for enhancing the expression of a protein selected from the group consisting of CFTR (cystic fibrosis transmembrane conductance regulator), V2-vasopressin receptor, LDL-receptor and HERG-K+-channel.

7. The use according to any one of the foregoing claims for the manufacture of a medicament for the treatment of a disease or condition selected from the group consisting of cystic fibrosis, diabetes insipidus, hypercholesterinaemia and long QT-syndrome-2.

8. Pharmaceutical composition, comprising Bortezomib and/or a pharmaceutically acceptable salt or ester thereof and a therapeutically effective amount of a compound stimulating deubiquitinating activity in a cell.

9. Pharmaceutical composition according to claim 8, characterized in that the compound stimulating deubiquitinating activity is selected from the group consisting of

a deubiquitinating enzyme

a nucleic acid sequence encoding a deubiquitinating enzyme.

10. Pharmaceutical composition according to claim 9, wherein the deubiquitinating enzyme is selected from the group consisting of ubiquitin carboxy-terminal hydrolases (UCH) and ubiquitin specific proteases (USP).

11. Pharmaceutical composition according to claim 9 or 10, characterized in that the deubiquitinating enzyme is USP-4.

12. A method for enhancing the expression of membrane proteins on a cell surface, comprising the step of treating the cell with a pharmaceutically effective amount of Bortezomib and/or a pharmaceutically acceptable salt or ester thereof.

13. Method according to claim 12, comprising the additional step of contacting the cell with a compound stimulating the deubiquitinating activity.

14. Method according to claim 13, wherein said compound increases the amount of deubiquitinating enzymes in the cell.

15. Method according to claim 14, wherein a compound selected from the group consisting of

a deubiquitinating enzyme and

a nucleic acid sequence encoding a deubiquitinating enzyme is introduced into the cell.

16. Method according to claim 15, wherein said deubiquitinating enzyme is selected from the group consisting of ubiquitin carboxy-terminal hydrolases (UCH) and ubiquitin specific proteases (USP).

17. Method according to claim 16, wherein the deubiquitinating enzyme is USP-4.

18. Method according to any one of claims 12 to 17, for enhancing the expression of a protein selected from the group consisting of CFTR (cystic fibrosis transmembrane conductance regulator), V₂-vasopressin receptor, LDL-receptor and HERG-K⁺-channel.

19. A method for treating a disease or condition selected from the group consisting of cystic fibrosis, diabetes insipidus, hypercholesterinaemia and long QT-syndrome-2, comprising the step of administering to a patient in need thereof a pharmaceutically effective amount of Bortezomib and/or a pharmaceutically effective salt or ester thereof.

20. Method according to claim 19, comprising the step of additionally administering to said patient a compound selected from the group consisting of

a deubiquitinating enzyme and

a nucleic acid sequence encoding a deubiquitinating enzyme.