Pharmaceutically acceptable salts of beta-guanidinopropionic acid with improved properties and uses thereof

Abstract

The present invention relates to new pharmaceutical salts of β-GPA which exhibit improved physical properties. In particular, the invention relates to salts of β-GPA with improved flow properties (e.g., improved Carr's index and/or Hausner ratio) such as fumarate salts, succinate salts, and oxalate salts. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of one or more salts of β-GPA, as well as methods of treating cancer including administration of a formulation including a β-GPA salt of the invention to a subject in need thereof.

1 . A method of treating cancer in a subject in need thereof, the method comprising administering an effective amount of a pharmaceutically acceptable salt of β-guanidinopropionic acid to the subject, wherein the pharmaceutically acceptable salt of β-guanidinopropionic acid is a 2:1 succinate salt, wherein the cancer is gastrointestinal, esophageal, colorectal, liver, pancreatic, or gastric cancer, or the cancer expresses CKB. 
     
     
         2 . The method of  claim 1 , wherein the cancer is gastrointestinal cancer. 
     
     
         3 . The method of  claim 2 , wherein the gastrointestinal cancer expresses CKB. 
     
     
         4 . The method of  claim 1 , wherein the cancer is esophageal cancer. 
     
     
         5 . The method of  claim 1 , wherein the cancer is colorectal cancer. 
     
     
         6 . The method of  claim 1 , wherein the cancer is liver cancer. 
     
     
         7 . The method of  claim 1 , wherein the cancer is pancreatic cancer. 
     
     
         8 . The method of  claim 1 , wherein the cancer is gastric cancer. 
     
     
         9 . The method of  claim 1 , wherein the cancer expresses CKB. 
     
     
         10 . The method of  claim 1 , wherein the cancer is metastatic cancer. 
     
     
         11 . The method of  claim 10 , wherein the effective amount comprises an amount effective to suppress metastatic colonization of the cancer. 
     
     
         12 . The method of  claim 1 , wherein the 2:1 succinate salt is administered prior to one or more therapeutically effective treatments or medical procedures. 
     
     
         13 . The method of  claim 1 , wherein the 2:1 succinate salt is administered subsequent to one or more therapeutically effective treatments or medical procedures. 
     
     
         14 . The method of  claim 12 , wherein the one or more therapeutically effective treatments comprises irinotecan, leucovorin, oxaliplatin, and/or 5-FU. 
     
     
         15 . The method of  claim 13 , wherein the one or more therapeutically effective treatments comprises irinotecan, leucovorin, oxaliplatin, and/or 5-FU.