Method for treating inflammation by administering a compound which binds LDL-receptor-related protein (LRP) ligand binding domain

Patent metadata

Field	Value
Publication number	US-9046537-B2
Application number	US-22186308-A
Country	US
Kind code	B2
Filing date	Aug 7, 2008
Priority date	Sep 22, 2003
Publication date	Jun 2, 2015
Grant date	Jun 2, 2015

Abstract

The present invention relates to the field of therapeutic methods, compositions and uses thereof, that affect, directly or indirectly, the behavior of LRP receptors. These compositions and methods result in the treatment of inflammatory, immunological and metabolic conditions. More particularly, the methods and compositions of the invention are directed to the identification of small molecules, drugs and/or pharmacological agents that affect the Wnt pathway by affecting normal complex formation among various signaling receptors, the LRP5 and LRP6 receptor, and related ligands.

First claim

The invention claimed is:

1. A method for treating inflammation in a subject, comprising the administration of a therapeutically effective amount of a compound to said subject, wherein said compound binds to an LDL-receptor-related protein (LRP) ligand binding domain, wherein the LRP is LRP-5 or LRP-6 and the ligand is selected from Dickkopf protein (Dkk) or sclerostm, and wherein said compound is a cyclic molecule or a heterocyclic organic molecule.

2. The method of claim 1 , wherein said inflammation is caused by an autoimmune disease or a chronic inflammatory disease.

3. The method of claim 2 , Wherein said inflammation is caused by Acute disseminated encephalomyelitis, Addison's disease, Ankylosing spondylitis, Antiphospholipid antibody syndrome, Aplastic anemia, Autoimmune hepatitis, Autoimmune Oophoritis, Coeliac disease, Crohn's disease, Diabetes mellitus, Gestational pemphigoid, Goodpasture's syndrome, Grave's disease, Guilian-Barre syndrome, Hashimoto's disease, Idiopathic thrombocytopenic purpura, Lupus erythematosus, Multiple sclerosis, Myasthenia gravis, Opsoclonus myoclonus syndrome, Optic neuritis, Ord's thyroiditis, Pemphigus, Pernicious anemia, Polyarthritis, Primary biliary cirrhosis, Rheumatoid arthritis, Reiter's syndrome, Sjogren's syndrome, Takayasu's arteritis, Warm autoimmune hemolytic anemia, or Wegener's granulomatosis.

4. The method of claim 2 , wherein said inflammation is caused by Tuberculosis, Chronic cholecystitis, Bronehiectasis, ulcerative colitis, silicosis or another pneumoconiosis disease.

5. The method of claim 1 , wherein said inflammation is caused by Crohn's disease or periodontitis.

6. The method of claim 1 , wherein said compound is:

7. A method of treating inflammation caused by Crohn's disease in a subject comprising administration of a therapeutically effective amount of a compound to the subject selected from

wherein said compound binds to an LDL-receptor-related protein (LRP) ligand binding domain, wherein the LRP is LRP-5 or LRP-6 and the ligand is selected from Dkk or sclerostin.

Assignees

• Rabbani Elazar
• Li Xiaofeng
• Liu Dakai
• Zhang Yazhou
• Jin Richard
• Bhattacharyya Riddhi
• Cheng Wei
• Donegan James J
• Enzo Biochem Inc

Inventors

• Rabbani Elazar
• Li Xiaofeng
• Liu Dakai
• Zhang Yazhou
• Jin Richard
• Bhattacharyya Riddhi
• Cheng Wei
• Donegan James J

Classifications

• G01N33/564

  for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9} · CPC title

• G01N33/5041

  involving analysis of members of signalling pathways · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · 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

• A61K31/535

  having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines · CPC title