Novel treatment of prostate carcinoma

Abstract

Disclosed herein are naphthoquinone analogs, such as plumbagin, pharmaceutical compositions that include naphthoquinone analogs, such as plumbagin, and methods of treating diseases and/or conditions such as cancer with naphthoquinone analogs, such as plumbagin. Also included are combination therapies wherein a naphthoquinone analog, such as plumbagin, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.

What is claimed is: 
     
         1 . (canceled) 
     
     
         2 . A composition comprising:
 a compound of Formula (I) or a pharmaceutically acceptable salt of Formula (I):   
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is hydrogen, R 3  is —OH, and R6 is hydrogen or —OH; or R 1  is methyl, R 3  is hydrogen, and R6 is hydrogen; 
         R 2  is hydrogen; 
         R 4  is hydrogen; and 
         R 5  is hydrogen. 
       
     
     
         3 . The composition of  claim 2 , wherein the compound of Formula (I) is juglone. 
     
     
         4 . The composition of  claim 2 , wherein the compound of Formula (I) is naphthazarin. 
     
     
         5 . The composition of  claim 2 , wherein the compound of Formula (I) is menadione. 
     
     
         6 . The composition of  claim 2 , wherein said composition is provided in a product combination, which comprises an androgen deprivation therapy agent that reduces the production of testosterone. 
     
     
         7 . The composition of  claim 6 , wherein the androgen deprivation therapy agent is selected from the group consisting of finasteride, leuprolide, triptorelin, goserelin, abarelix, degarelix, and abiraterone. 
     
     
         8 . The composition of  claim 6 , wherein the androgen deprivation therapy agent decreases the subject's serum testosterone level to about 5-20% of a healthy male subject. 
     
     
         9 . The composition of  claim 6 , wherein said product combination inhibits the growth of prostate cancer. 
     
     
         10 . The composition of  claim 6 , wherein said product combination inhibits or delays the onset of castration-resistant prostate cancer. 
     
     
         11 . The composition of  claim 6 , wherein the compound of Formula (I) is formulated for oral administration. 
     
     
         12 . The composition of  claim 6 , wherein the compound of Formula (I) and the androgen deprivation therapy agent are formulated in a single formulation or a single dosage. 
     
     
         13 . The composition of  claim 6 , wherein the androgen deprivation therapy agent is formulated for oral administration. 
     
     
         14 . The composition of  claim 6 , wherein the compound of Formula (I) and the androgen deprivation therapy agent are formulated for oral administration. 
     
     
         15 . The composition of  claim 9 , wherein said prostate cancer is androgen dependent prostate cancer. 
     
     
         16 . The composition of  claim 6 , wherein the androgen deprivation therapy agent decreases the subject's serum testosterone level to at least about ≤50 ng/dL. 
     
     
         17 . The composition of  claim 6 , wherein the androgen deprivation therapy agent decreases the subject's serum testosterone level to at least about ≤20 ng/dL. 
     
     
         18 . The composition of  claim 6 , wherein the product combination results in a decrease in prostate cancer tumor size. 
     
     
         19 . A method of inhibiting or delaying the growth of prostate cancer, comprising administering to a subject having prostate cancer a therapeutically effective amount of a composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt of Formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is hydrogen, R 3  is —OH, and R6 is hydrogen or —OH; or R 1  is methyl, R 3  is hydrogen, and R6 is hydrogen; 
         R 2  is hydrogen; 
         R 4  is hydrogen; and 
         R 5  is hydrogen. 
       
     
     
         20 . The method of  claim 19 , wherein the compound of Formula (I) is juglone. 
     
     
         21 . The method of  claim 19 , wherein the compound of Formula (I) is naphthazarin. 
     
     
         22 . The method of  claim 19 , wherein the compound of Formula (I) is menadione. 
     
     
         23 . The method of  claim 19 , wherein the compound of Formula (I) is administered to the subject in combination with, subsequent to, or concomitantly with, an androgen deprivation therapy that reduces the production of testosterone; and wherein the growth of prostate cancer is inhibited or delayed. 
     
     
         24 . The method of  claim 23 , wherein the androgen deprivation therapy is surgical orchiectomy. 
     
     
         25 . The method of  claim 23 , wherein the androgen deprivation therapy comprises administration of a compound selected from the group consisting of finasteride, leuprolide, triptorelin, goserelin, abarelix, degarelix, and abiraterone. 
     
     
         26 . The method of  claim 23 , wherein the androgen deprivation therapy decreases the subject's serum testosterone level to about 5-20% of a healthy male subject. 
     
     
         27 . The method of  claim 23 , wherein said method inhibits the growth of prostate cancer. 
     
     
         28 . The method of  claim 23 , wherein said method inhibits or delays the onset of castration-resistant prostate cancer. 
     
     
         29 . The method of  claim 23 , wherein the compound of Formula (I) is administered to the subject orally. 
     
     
         30 . The method of  claim 23 , wherein the androgen deprivation therapy is administered to the subject orally. 
     
     
         31 . The method of  claim 23 , wherein the compound of Formula (I) and the androgen deprivation therapy are administered to the subject orally. 
     
     
         32 . The method of  claim 23 , wherein said prostate cancer is androgen dependent prostate cancer. 
     
     
         33 . The method of  claim 23 , wherein said prostate cancer is castration-resistant prostate cancer. 
     
     
         34 . The method of  claim 23 , wherein the androgen deprivation therapy decreases the subject's serum testosterone level to at least about ≤50 ng/dL. 
     
     
         35 . The method of  claim 23 , wherein the androgen deprivation therapy decreases the subject's serum testosterone level to at least about ≤20 ng/dL. 
     
     
         36 . The method of  claim 23 , wherein the method results in a decrease in prostate cancer tumor size.