US2003082666A1PendingUtilityA1

Method of treating autoimmune diseases

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Priority: Nov 21, 2000Filed: Jul 2, 2002Published: May 1, 2003
Est. expiryNov 21, 2020(expired)· nominal 20-yr term from priority
Inventors:Gary KammerNilamadhab Mishra
A61P 37/00G01N 2500/04A61K 31/165A61K 31/336A61K 31/22A61K 31/407A61K 31/18C12Q 1/44A61K 31/19A61K 31/70A61P 17/14A61K 31/17A61K 31/167A61K 31/473A61K 31/166A61K 31/16A61K 31/00A61K 31/4406A61K 31/222A61K 31/4353A61K 31/192
40
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Claims

Abstract

A method of treating an autoimmune disease (for example, Systemic Lupus Erythematosus) comprises administering to the subject a treatment effective amount of a histone hyperacetylating agent, or a pharmaceutically acceptable salt thereof. Methods of screening compounds useful for the treatment of autoimmune disease are also disclosed.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of treating an autoimmune disease in a subject in need thereof, comprising administering to said subject a treatment effective amount of a histone hyperactylating agent, or a pharmaceutically acceptable salt thereof.  
     
     
         2 . A method according to  claim 1 , wherein said histone hyperacetylating agent is a histone deacetylase inhibitor.  
     
     
         3 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of Trichostatin A and Trichostatin C.  
     
     
         4 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of Oxamflati, Trapoxin A, FR901228, Apicidin, HC-Toxin, WF27082, and Chlamydocin.  
     
     
         5 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of Salicylihydroxamic Acid, Suberoylanilide Hydroxamic Acid, and Azelaic Bishydroxamic Acid.  
     
     
         6 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of Azelaic-1-Hydroxamate-9-Anilide, M-Carboxycinnamic Acid Bishydroxamide, 6-(3-Chlorophenylureido)carpoic Hydroxamic Acid, MW2796, and MW2996.  
     
     
         7 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of Sodium Butyrate, Isovalerate, Valerate, 4-Phenylbutyrate, Phenylbutyrate, Propionate, Butrymide, Isobutyramide, Phenylacetate, 3-Bromopropionate, and Tributyrin.  
     
     
         8 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of MS-27-275 and the 3′-amino derivative thereof.  
     
     
         9 . A method according to  claim 1 , wherein said histone hyperacetylating agent is selected from the group consisting of Depudecin and Scriptaid.  
     
     
         10 . A method according to  claim 1 , wherein said autoimmune disease is selected from the group consisting of rheumatoid arthritis, Sjogren's disease, polymyositis, and dermatomyositis.  
     
     
         11 . A method of treating systemic lupus erythematosus in a subject in need thereof, comprising administering to said subject a treatment effective amount of a histone hyperactylating agent, or a pharmaceutically acceptable salt thereof.  
     
     
         12 . A method according to  claim 11 , wherein said histone hyperacetylating agent is a histone deacetylase inhibitor.  
     
     
         13 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of Trichostatin A and Trichostatin C.  
     
     
         14 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of Oxamflati, Trapoxin A, FR901228, Apicidin, HC-Toxin, WF27082, and Chlamydocin.  
     
     
         15 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of Salicylihydroxamic Acid, Suberoylanilide Hydroxamic Acid, and Azelaic Bishydroxamic Acid.  
     
     
         16 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of Azelaic-1-Hydroxamate-9-Anilide, M-Carboxycinnamic Acid Bishydroxamide, 6-(3-Chlorophenylureido)carpoic Hydroxamic Acid, MW2796, and MW2996.  
     
     
         17 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of Sodium Butyrate, Isovalerate, Valerate, 4-Phenylbutyrate, Phenylbutyrate, Propionate, Butrymide, Isobutyramide, Phenylacetate, 3-Bromopropionate, and Tributyrin.  
     
     
         18 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of MS-27-275 and the 3′-amino derivative thereof.  
     
     
         19 . A method according to  claim 11 , wherein said histone hyperacetylating agent is selected from the group consisting of Depudecin and Scriptaid.  
     
     
         20 . A method of screening compounds for activity in treating an autoimmune disease, comprising: 
 (a) contacting a histone deacetylase, or an extract containing histone deacetylase with (i) a known amount of a labeled compound that interacts with a histone deacetylase; and (ii) a known dilution of a test compound or natural product extract; and    (b) determining the inhibition of interaction of said labeled compound with said histone deacetylase induced by said test compound, where the inhibition of interaction of said labeled compound with said histone deacetylase indicates said compound or extract is a candidate for the treatment of an autoimmune disease.    
     
     
         21 . A method according to  claim 20 , wherein said histone deacetylase is mammalian histone deacetylase.  
     
     
         22 . A method according to  claim 20 , wherein said histone deacetylase is human histone deacetylase.  
     
     
         23 . A method according to  claim 20 , wherein said labeled compound binds to histone deacetylase.  
     
     
         24 . A method according to  claim 20 , wherein said labeled compound is a substrate of histone deacetylase.  
     
     
         25 . A method according to  claim 20 , wherein said autoimmune disease is systemic lupus erythematosus.  
     
     
         26 . A method of screening compounds for activity in treating an autoimmune disease, comprising: 
 contacting an intact host cell with a test compound or a natural product extract; and then    determining the level of histone acetylation in said cell, wherein elevated levels of histone acetylation indicates said compound or extract is a candidate for the treatment of an autoimmune disease.    
     
     
         27 . A method according to  claim 26 , wherein said cell is a mammalian cell.  
     
     
         28 . A method according to  claim 26 , wherein said cell is a human cell.  
     
     
         29 . A method according to  claim 26 , wherein said autoimmune disease is systemic lupus erythematosus.

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