Lipopeptides for use in treating liver diseases and cardiovascular diseases

Patent metadata

Field	Value
Publication number	US-10413585-B2
Application number	US-201314442304-A
Country	US
Kind code	B2
Filing date	Nov 12, 2013
Priority date	Nov 12, 2012
Publication date	Sep 17, 2019
Grant date	Sep 17, 2019

Abstract

The present invention relates to lipopeptide-based compounds for use in the diagnosis, prevention and/or treatment of a liver disease or condition, preferably liver involved metabolic diseases, as well as in the control or modification of the cholesterol level or cholesterol uptake and, thus, diagnosis, prevention and/or treatment of a cardiovascular disease. The present invention furthermore relates to an in vitro or in vivo assay or method for testing or measuring the NTCP-mediated transport of test compound(s). The present invention furthermore relates to a method for the diagnosis, prevention and/or treatment of a liver disease or condition, comprising administering a therapeutically effective amount of a lipopeptide-based compound to a patient. The present invention furthermore relates to a method for the diagnosis, prevention and/or treatment of a cardiovascular disease.

First claim

The invention claimed is:

1. A method for treating a cardiovascular disease (CVD) in a patient, the method comprising administering a therapeutically effective amount of a lipopeptide to the patient,
wherein the lipopeptide comprises the sequence selected from SEQ ID NOs: 2 to 12, 14, 18 to 20, and 22, and wherein the lipopeptide comprises an N-terminal myristoylation and a C-terminal hydrophobic modification.

2. The method of claim 1 , wherein said administering the lipopeptide causes control or modification of cholesterol level or cholesterol uptake, and
wherein the cholesterol level or uptake is controlled or modified by decreasing or blocking the NCTP-mediated bile salt transport by the lipopeptide.

3. The method of claim 1 , comprising administering the lipopeptide via a route selected from subcutaneous, intravenous, oral, nasal, intramuscular, transdermal, inhalative, and suppository.

4. A method for reducing taurocholate uptake in liver cells of a human, the method comprising administering to the human an effective amount of a lipopeptide comprising the sequence selected from SEQ ID NOs: 2 to 12, 14, 18 to 20, and 22, and wherein the lipopeptide comprises an N-terminal myristoylation and a C-terminal hydrophobic modification.

5. The method of claim 4 , comprising administering the lipopeptide via a route selected from subcutaneous, intravenous, oral, nasal, intramuscular, transdermal, inhalative, and suppository.

6. The method of claim 1 , wherein the C-terminal hydrophobic modification comprises conjugation of the lipopeptide to a moiety selected from cholesterol, phospholipid, gycolipid, glycerol ester, steroid, ceramid, isoprene, adamantine, fernesol, aliphatic group, polyaromatic compound, acyl group, bile salt, and a bile salt conjugate.

7. The method of claim 6 , wherein the acyl group is oleic acid.

8. The method of claim 6 , wherein the C-terminal hydrophobic modification comprises conjugation of the lipopeptide to the moiety via a covalent bond.

9. The method of claim 8 , wherein the covalent bond is a carbamate, amide, ether, or disulfide bond.

10. The method of claim 1 , wherein the lipopeptide comprises the sequence of SEQ ID NO: 18.

11. The method of claim 1 , wherein the lipopeptide comprises the sequence of SEQ ID NO: 19.

12. The method of claim 1 , wherein the lipopeptide comprises the sequence of SEQ ID NO: 20.

13. The method of claim 4 , wherein the C-terminal hydrophobic modification comprises conjugation of the lipopeptide to a moiety selected from cholesterol, phospholipid, gycolipid, glycerol ester, steroid, ceramid, isoprene, adamantine, fernesol, aliphatic group, polyaromatic compound, acyl group, bile salt, and a bile salt conjugate.

14. The method of claim 13 , wherein the acyl group is oleic acid.

15. The method of claim 13 , wherein the C-terminal hydrophobic modification comprises conjugation of the lipopeptide to the moiety via a covalent bond.

16. The method of claim 15 , wherein the covalent bond is a carbamate, amide, ether, or disulfide bond.

17. The method of claim 4 , wherein the lipopeptide comprises the sequence of SEQ ID NO: 18.

18. The method of claim 4 , wherein the lipopeptide comprises the sequence of SEQ ID NO: 19.

19. The method of claim 4 , wherein the lipopeptide comprises the sequence of SEQ ID NO: 20.

Assignees

• Univ Heidelberg Ruprecht Karls
• Cleeves Volker

Inventors

• Cleeves Volker
• Urban Stephan
• Kubitz Ralf

Classifications

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/575

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title

• G01N33/92

  involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} · CPC title

• G01N2500/10

  involving cells · CPC title