Novel chemical entities affecting neuroblastoma tumor-initiating cells

Abstract

Disclosed are neuroblastoma tumor-initiating cell inhibiting compositions comprising chemical entities capable of affecting neuroblastoma tumor-initiating cells. Pharmaceutical preparations that include these chemical entities are also provided for the treatment of neuroblastoma. These pharmaceutical preparations are suitable for the treatment of humans, and are particularly suited for the treatment of children of 12 years of age or younger having neuroblastoma. The compositions and pharmaceutical preparations posses reduced normal cell cytotoxicity. The compositions and pharmaceutical preparations may be used alone or together with other conventional neuroblastoma preparations as part of a clinical regimen in the treatment and management of neuroblastoma.

1 . A neuroblastoma inhibiting composition comprising a chemical entity that selectively affects neuroblastoma tumor-initiating cells, said composition comprising one or more active ingredients comprising: 
 2.3-Dimethoxy-1.4-naphthoquinone,    Aklavine Hydrochloride,    Amodiaquin dihydrochloride dehydrate;    Amsacrine Hydrochloride;    Azaguanine-8;    beta-peltatin;    Camptothecine (S.+);    CGP-74514A hydrochloride;    Chelerythrine chloride;    Cholestan-3beta.5alpha.6beta-Triol;    Ciclopirox Olamine;    Clofazimine;    Colchicine;    Convallatoxin;    Crassin Acetate;    Crinamine;    Dequalinium analog. C-14 linker;    Dequalinium dichloride;    Digitoxin;    Digoxigenin;    Dihydrogambogic acid;    Dihydroouabain;    Erysolin;    Gambogic acid;    Mechlorethamine;    Meclizine hydrochloride;    MG 624;    Mitoxanthrone Hydrochloride;    Ouabain;    Oxybendazole;    Oxybendazole;    Paclitaxel;    Parthenolide;    Patulin;    Periplocymarin;    Peruvoside;    Primaquine diphosphate;    Quinacrine dihydrochloride;    Sanguinarine chloride; or    Tomatine.    
   
   
       2 . The neuroblastoma-inhibiting composition of  claim 1  further comprising ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, vincristine sulfate, or a combination thereof.  
   
   
       3 . The neuroblastoma inhibiting composition of  claim 1  further defined as having reduced non-neuroblastoma tumor-initiating cell cytotoxicity.  
   
   
       4 . The neuroblastoma inhibiting composition of  claim 1  further defined as essentially free of non-neuroblastoma tumor cell inhibiting activity.  
   
   
       5 . A pharmaceutical formulation for the inhibition of neuroblastoma comprising an effective amount of a neuroblastoma tumor-initiating cell inhibiting composition, said composition comprising one or more active ingredients comprising: 
 2.3-Dimethoxy-1.4-naphthoquinone,    Aklavine Hydrochloride,    Amodiaquin dihydrochloride dehydrate;    Amsacrine Hydrochloride;    Azaguanine-8;    beta-peltatin;    Camptothecine (S.+);    CGP-74514A hydrochloride;    Chelerythrine chloride;    Cholestan-3beta.5alpha.6beta-Triol;    Ciclopirox Olamine;    Clofazimine;    Colchicine;    Convallatoxin;    Crassin Acetate;    Crinamine;    Dequalinium analog. C-14 linker;    Dequalinium dichloride;    Digitoxin;    Digoxigenin;    Dihydrogambogic acid;    Dihydroouabain;    Erysolin;    Gambogic acid;    Mechlorethamine;    Meclizine hydrochloride;    MG 624;    Mitoxanthrone Hydrochloride;    Ouabain;    Oxybendazole;    Oxybendazole;    Paclitaxel;    Parthenolide;    Patulin;    Periplocymarin;    Peruvoside;    Primaquine diphosphate;    Quinacrine dihydrochloride;    Sanguinarine chloride; or    Tomatine.    
   
   
       6 . The pharmaceutical formulation of  claim 5  further comprising ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, vincristine sulfate, or a combination thereof.  
   
   
       7 . The pharmaceutical preparation of  claim 6  further comprising a pharmaceutically acceptable carrier solution.  
   
   
       8 . A method for inhibiting neuroblastoma tumor-initiating cells comprising administering an effective amount of a composition comprising a neuroblastoma tumor-initiating cell inhibiting ingredient.  
   
   
       9 . The method of  claim 8  wherein said neuroblastoma tumor-initiating cell inhibiting ingredient comprises one or more active ingredients comprising: 
 2.3-Dimethoxy-1.4-naphthoquinone,    Aklavine Hydrochloride,    Amodiaquin dihydrochloride dehydrate;    Amsacrine Hydrochloride;    Azaguanine-8;    beta-peltatin;    Camptothecine (S.+);    CGP-74514A hydrochloride;    Chelerythrine chloride;    Cholestan-3beta.5alpha.6beta-Triol;    Ciclopirox Olamine;    Clofazimine;    Colchicine;    Convallatoxin;    Crassin Acetate;    Crinamine;    Dequalinium analog. C-14 linker;    Dequalinium dichloride;    Digitoxin;    Digoxigenin;    Dihydrogambogic acid;    Dihydroouabain;    Erysolin;    Gambogic acid;    Mechlorethamine;    Meclizine hydrochloride;    MG 624;    Mitoxanthrone Hydrochloride;    Ouabain;    Oxybendazole;    Oxybendazole;    Paclitaxel;    Parthenolide;    Patulin;    Periplocymarin;    Peruvoside;    Primaquine diphosphate;    Quinacrine dihydrochloride;    Sanguinarine chloride; or    Tomatine.    
   
   
       10 . The method of  claim 8  wherein the effective amount of the neuroblastoma tumor initiating cell inhibiting ingredient is an amount effective to arrest growth of neuroblastoma tumor-initiating cells.  
   
   
       11 . The method of  claim 8  wherein the composition further comprises ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, vincristine sulfate, or a combination thereof.  
   
   
       12 . The method of  claim 8  wherein the neuroblastoma tumor-initiating cells are in an animal having neuroblastoma.  
   
   
       13 . The method of  claim 8  wherein the composition has a reduced non-neuroblastoma tumor-initiating cell cytotoxicity.  
   
   
       14 . The method of  claim 8  wherein the composition is essentially free of non-neuroblastoma tumor cell inhibiting activity.  
   
   
       15 . A method for inhibiting neuroblastoma in an animal comprising administering an effective amount of a composition comprising a neuroblastoma tumor-initiating cell inhibiting ingredient.  
   
   
       16 . The method of  claim 15  wherein said neuroblastoma tumor-initiating cell inhibiting ingredient comprises one or active ingredients comprising: 
 2.3-Dimethoxy-1.4-naphthoquinone,    Aklavine Hydrochloride,    Amodiaquin dihydrochloride dehydrate;    Amsacrine Hydrochloride;    Azaguanine-8;    beta-peltatin;    Camptothecine (S.+);    CGP-74514A hydrochloride;    Chelerythrine chloride;    Cholestan-3beta.5alpha.6beta-Triol;    Ciclopirox Olamine;    Clofazimine;    Colchicine;    Convallatoxin;    Crassin Acetate;    Crinamine;    Dequalinium analog. C-14 linker;    Dequalinium dichloride;    Digitoxin;    Digoxigenin;    Dihydrogambogic acid;    Dihydroouabain;    Erysolin;    Gambogic acid;    Mechlorethamine;    Meclizine hydrochloride;    MG 624;    Mitoxanthrone Hydrochloride;    Ouabain;    Oxybendazole;    Oxybendazole;    Paclitaxel;    Parthenolide;    Patulin;    Periplocymarin;    Peruvoside;    Primaquine diphosphate;    Quinacrine dihydrochloride;    Sanguinarine chloride; or    Tomatine.    
   
   
       17 . The method of  claim 15  wherein the composition further comprises ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, vincristine sulfate, or a combination thereof.  
   
   
       18 . The method of  claim 15  wherein the animal is a human of 12 years of age or younger.  
   
   
       19 . The method of  claim 15  wherein the composition is essentially free of non-neuroblastoma tumor-initiating cell inhibiting activity.  
   
   
       20 . The method of  claim 15  wherein the effective amount of the composition is further described as an amount effective to arrest growth of neuroblastoma tumor-initiating cells.