Template-fixed peptidomimetics

Patent metadata

Field	Value
Publication number	US-10787486-B2
Application number	US-201816190459-A
Country	US
Kind code	B2
Filing date	Nov 14, 2018
Priority date	Feb 28, 2007
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

The template-fixed β-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

First claim

The invention claimed is:

1. A method of treatment, wherein the treatment is selected from the group consisting of
slowing or halting viral progression in a subject infected with HIV;
treating cancer mediated by or resulting from CXCR4 receptor activity in a subject in need thereof, wherein said cancer is brain cancer, prostate cancer, lung cancer, kidney cancer, neuroblastoma, non-Hodgkin's lymphoma, ovarian cancer, multiple myeloma, pancreatic cancer, or melanoma;
treating an immunological disease mediated by or resulting from CXCR4 receptor activity in a subject in need thereof;
treating immunosuppression in a subject in need thereof;
treating an inflammatory disorder in a subject in need thereof; and
stem cell mobilization of mesenchymal stem cells (MSC) which retention depends on the CXCR4-receptor in a subject in need thereof;

the method comprising:
administering a therapeutically effective amount of a Cyclo(-Tyr-His-X-Cys-Ser-Ala- D Pro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys- D Pro-Pro) compound having a disulfide bond between Cys4 and Cys11, or a pharmaceutically acceptable salt thereof, wherein X is Ala or Tyr to the subject.

2. The method of claim 1 , wherein the administering is oral, topical, transdermal, injection, buccal, transmucosal, pulmonary or inhalation administration.

3. The method of claim 1 , wherein the compound is administered in a composition further comprising a pharmaceutically inert carrier and wherein the composition is in the form of a tablet, a dragee, a capsule, a solution, a liquid, a gel, a plaster, a cream, an ointment, a syrup, a slurry, a suspension, a spray, a nebulizer, or a suppository.

4. The method of claim 1 , wherein the immunosuppression is induced by graft/transplantation rejection.

5. The method of claim 1 , wherein the inflammatory disorder is selected from the group consisting of asthma, allergic rhinitis, hypersensitivity lung diseases, hypersensitivity pneumonitis, eosinophilic pneumonias, delayed-type hypersensitivity, interstitial lung disease (ILD), idiopathic pulmonary fibrosis, ILD associated with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, peripheral vascular disease, systemic sclerosis, Sjögren's syndrome, von Hippel Lindau disease, systemic anaphylaxis or hypersensitivity responses, drug allergies, rheumatoid arthritis, psoriatic arthritis, Behcet's Syndrome, mucositis, Crohn's disease, multiple sclerosis, myasthenia gravis, juvenile onset diabetes, glomerulonephritis, autoimmune thyroiditis, graft rejection, inflammatory bowel diseases, and inflammatory dermatoses.

6. The method of claim 5 , wherein the graft rejection is allograft rejection or graft-versus-host disease.

7. The method of claim 1 , wherein X is Ala.

8. The method of claim 1 , wherein X is Tyr.

Assignees

• Univ Zuerich
• Polyphor Ltd

Inventors

• Obrecht Daniel
• Gombert Frank
• Demarco Steven J
• Ludin Christian
• Vrijbloed Jan Wim
• Moehle Kerstin
• Robinson John-Anthony
• Mukherjee Reshmi
• Henze Heiko
• Romagnoli Barbara

Classifications

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K7/56 Primary

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• A61P31/18

  for HIV · CPC title

• C07K7/64

  Cyclic peptides containing only normal peptide links · CPC title

• A61P31/12

  Antivirals · CPC title