Novel compounds and compositions for targeting cancer stem cells

Abstract

The invention provides naphthofuran compounds, polymorphs of naphthofuran compounds, naphthofuran compounds in particle form, purified compositions that contain one or more naphthofuran compounds, purified compositions that contain one or more naphthofuran compounds in particle form, methods of producing these naphthofuran compounds, polymorphs, purified compositions and/or particle forms, and methods of using these naphthofuran compounds, polymorphs, purified compositions and/or particle forms to treat subjects in need thereof.

What is claimed is: 
     
         1 . A composition comprising a purified form of compound 1, a salt, solvate, hydrate, or prodrug thereof, 
       
         
           
           
               
               
           
         
         wherein the composition has a purity greater than or equal to 95.0% as determined by high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) or both HPLC and NMR, 
         and wherein the composition comprises less than or equal to 5% impurities. 
       
     
     
         2 . The composition of  claim 1 , wherein the composition has a purity greater than or equal to 99% as determined by HPLC, NMR or both HPLC and NMR. 
     
     
         3 . The composition of  claim 1 , wherein the composition comprises less than or equal to 0.2% of each single impurity. 
     
     
         4 . The composition of  claim 1 , wherein the impurities comprise a residual solvent selected from the group consisting of ethyl acetate (EtOAc), toluene, ethanol, methanol, chloroform, and CH 2 Cl 2 /hexane. 
     
     
         5 . The composition of  claim 1 , wherein the compound is in particle form and the particles comprise the compound in a crystalline state. 
     
     
         6 . A compound having the structure shown below, a salt, solvate, hydrate, or prodrug thereof, 
       
         
           
           
               
               
           
         
         wherein the compound is in a particle form, and wherein the particle has a diameter of less than or equal to about 20 micrometers. 
       
     
     
         7 . A pharmaceutical composition comprising a population of particles of the compound of  claim 6 , wherein a fraction of the cumulative total of the particles have a diameter in the range of 0.2 μm to 20 μm. 
     
     
         8 . A pharmaceutical composition comprising a population of particles of the compound of  claim 6 , wherein 50% of the cumulative total of the particles (D50) have a diameter of about 2 μm. 
     
     
         9 . The pharmaceutical composition of  claim 8 , further comprising a pharmaceutically acceptable excipient. 
     
     
         10 . A method of treating a cancer in a human subject, the method comprising administering to a human subject in need thereof a therapeutically effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 10 , wherein the cancer is selected from the group consisting of colorectal adenocarcinoma, breast cancer, ovarian cancer, head and neck cancer, melanoma, angiosarcoma, gastric adenocarcinoma, lung cancer, refractory cancer, recurrent cancer, metastatic cancer, and adrenocorticoid. 
     
     
         12 . The method of  claim 10 , wherein the cancer is associated with overexpression of STAT3. 
     
     
         13 . A method of prolonging progression free survival (PFS) in a cancer patient, the method comprising administering to a human subject in need thereof a therapeutically effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 13 , wherein the cancer is selected from the group consisting of colorectal adenocarcinoma, breast cancer, ovarian cancer, head and neck cancer, melanoma, angiosarcoma, gastric adenocarcinoma, lung cancer, refractory cancer, recurrent cancer, metastatic cancer, and adrenocorticoid. 
     
     
         15 . The method of  claim 13 , wherein the cancer is associated with overexpression of STAT3.