Brca1-based breast or ovarian cancer prevention agents and methods of use

Abstract

A pharmaceutical composition for use in treating, inhibiting, and/or preventing breast and/or ovarian cancer can include: a molecule having a structure of one of Compounds 1-38, pharmaceutically acceptable salt thereof, or analog thereof, and a pharmaceutically acceptable carrier containing the compound. The pharmaceutically acceptable carrier can be configured for oral, systemic, transdermal, intranasal, suppository, parenteral, intramuscular, intravenous, or subcutaneous administration. The compound can be present in the composition in a therapeutically effective amount for treating, inhibiting, and/or preventing breast and/or ovarian cancer. Also, the compound can be present in a therapeutically effective amount for enhancing production of BRCA1.

1 . A pharmaceutical composition for use in treating, inhibiting, and/or preventing breast and/or ovarian cancer, the composition comprising:
 a molecule having a structure of one of Compounds 1-38, pharmaceutically acceptable salt thereof, or analog thereof; and   a pharmaceutically acceptable carrier containing the compound.   
   
   
       2 . A composition as in  claim 1 , wherein the pharmaceutically acceptable carrier is for oral, systemic, transdermal, intranasal, suppository, parenteral, intramuscular, intravenous, or subcutaneous administration. 
   
   
       3 . A composition as in  claim 1 , wherein the compound is present in a therapeutically effective amount for treating, inhibiting, and/or preventing breast and/or ovarian cancer. 
   
   
       4 . A composition as in  claim 1 , wherein the compound is present in a therapeutically effective amount for enhancing production of BRCA1 
   
   
       5 . A composition as in  claim 1 , wherein the molecule has a structure of Compound 10. 
   
   
       6 . A pharmaceutical composition for use in treating, inhibiting, and/or preventing breast and/or ovarian cancer, the composition comprising:
 a compound having one of Formula B, Formula C, or pharmaceutically acceptable salt thereof that enhances production of BRCA1;   
     
       
         
         
             
             
         
       
       wherein: X is independently selected from N, NH, N-alkyl, O, or S; 
       Y is selected from C, or N; 
       R 1  is a substituted or unsubstituted heterocycle selected from 2-furan, 3-furan, 2-thiophene, 3-thiophene, 2-pyrrole, 3-pyrrole, 2-oxazole, 4-oxazole, 5-oxazole, 2-thiazole, 4-thiazole, 5-thiazole, 2-imidazole, 4-imidazole, 5-imidazole, 3-isoxazole, 4-isoxazole, 5-isoxazole, 3-isothiazole, 4-isothiazole, 5-isothiazole, 4-(1,2,3) oxadiazole, 5-(1,2,3) oxadiazole, 4-(1,2,3) triazole, 5-(1,2,3) triazole, or 2-(1,3,4) thiadiazole, where the substituted heterocycle is substituted at any position with H, a halogen, Cl, F, CH 3 , CH 3 CH 2 , or higher or lower substituted or unsubstituted straight chain or branched aliphatic; 
       R 2  is a substituted or unsubstituted cycle or heterocycle selected from phenyl, 2-furan, 3-furan, 2-thiophene, 3-thiophene, 2-pyrrole, 3-pyrrole, 2-oxazole, 4-oxazole, 5-oxazole, 2-thiazole, 4-thiazole, 5-thiazole, 2-imidazole, 4-imidazole, 5-imidazole, 3-isoxazole, 4-isoxazole, 5-isoxazole, 3-isothiazole, 4-isothiazole, 5-isothiazole, 4-(1,2,3) oxadiazole, 5-(1,2,3) oxadiazole, 4-(1,2,3) triazole, 5-(1,2,3) triazole, or 2-(1,3,4) thiadiazole, where the substituted cycle or heterocycle is substituted at any position with H, a halogen, Cl, F, CH 3 , CH 3 CH 2 , or higher or lower substituted or unsubstituted straight chain or branched aliphatic; 
       Z is an amide, amine, imine, urea, thiourea, or thioamide functional group (either constitutional isomer, where possible); and 
       n=0, 1, 2, or 3. 
     
   
   
       7 . A composition as in  claim 6 , wherein the compound is present in a therapeutically effective amount for enhancing production of BRCA1. 
   
   
       8 . A pharmaceutical composition for use in treating, inhibiting, and/or preventing breast and/or ovarian cancer, the composition comprising:
 a compound having one of Formula D, Formula E, or pharmaceutically acceptable salt thereof that enhances production of BRCA1;   
     
       
         
         
             
             
         
       
       wherein: X 1  and X 2  are independently selected from C, N, NH, N-alkyl, O, or S; 
       Y 1 , Y 2 , and Y 3  are independently selected from C, or N; 
       R 1  is a substituted or unsubstituted heterocycle selected from 2-furan, 3-furan, 2-thiophene, 3-thiophene, 2-pyrrole, 3-pyrrole, 2-oxazole, 4-oxazole, 5-oxazole, 2-thiazole, 4-thiazole, 5-thiazole, 2-imidazole, 4-imidazole, 5-imidazole, 3-isoxazole, 4-isoxazole, 5-isoxazole, 3-isothiazole, 4-isothiazole, 5-isothiazole, 4-(1,2,3) oxadiazole, 5-(1,2,3) oxadiazole, 4-(1,2,3) triazole, 5-(1,2,3) triazole, or 2-(1,3,4) thiadiazole; 
       R 2  is a substituted or unsubstituted cycle or heterocycle selected from phenyl, 2-furan, 3-furan, 2-thiophene, 3-thiophene, 2-pyrrole, 3-pyrrole, 2-oxazole, 4-oxazole, 5-oxazole, 2-thiazole, 4-thiazole, 5-thiazole, 2-imidazole, 4-imidazole, 5-imidazole, 3-isoxazole, 4-isoxazole, 5-isoxazole, 3-isothiazole, 4-isothiazole, 5-isothiazole, 4-(1,2,3) oxadiazole, 5-(1,2,3) oxadiazole, 4-(1,2,3) triazole, 5-(1,2,3) triazole, or 2-(1,3,4) thiadiazole; 
       R 3  is a substituent on any one or more ring atoms independently selected from H, a halogen, Cl, F, Br, NO 2 , CH 3 , CH 3 CH 2 , or higher or lower substituted or unsubstituted straight chain or branched aliphatic; 
       Z is an amide, amine, imine, urea, thiourea, or thioamide functional group (either constitutional isomer, where possible); and 
       n=0, 1, 2, or 3; 
       where X 1  and X 2  are not both N-alkyl, O, S, or O and S together, N-alkyl and O together, or N-Alkyl and S together and the compound is not one of Compounds 1-32. 
     
   
   
       9 . A composition as in  claim 8 , wherein the compound is present in a therapeutically effective amount for enhancing production of BRCA1. 
   
   
       10 . A pharmaceutical composition for use in treating, inhibiting, and/or preventing breast and/or ovarian cancer, the composition comprising:
 a compound having one of Formula F, Formula G, or pharmaceutically acceptable salt thereof that enhances production of BRCA1;   
     
       
         
         
             
             
         
       
       where: X 1  and X 2  are independently selected from C, N, NH, N-alkyl, O, or S; 
       Y 1 , Y 2 , and Y 3  are independently selected from C, or N; 
       R 3 , R 4 , and R 5  are each a substituent on any one or more ring atoms independently selected from H, a halogen, Cl, F, Br, NO 2 , CH 3 , CH 3 CH 2 , or higher or lower substituted or unsubstituted straight chain or branched aliphatic; 
       Z is an amide, amine, imine, urea, thiourea, or thioamide functional group (either constitutional isomer, where possible); and 
       n=0, 1, 2, or 3; 
       where X 1  and X 2  are not both N-alkyl, O, S, or O and S together, N-alkyl and O together, or N-Alkyl and S together. 
     
   
   
       11 . A composition as in  claim 10 , wherein the compound is present in a therapeutically effective amount for enhancing production of BRCA1. 
   
   
       12 . A pharmaceutical composition for use in treating, inhibiting, and/or preventing breast and/or ovarian cancer, the composition comprising:
 a compound having one of Formula H, Formula I, or pharmaceutically acceptable salt thereof that enhances production of BRCA1;   
     
       
         
         
             
             
         
       
       where: X 1  and X 2  are independently selected from C, N, NH, N-alkyl, O, or S; 
       Y 1 , Y 2 , and Y 3  are independently selected from C, or N; 
       Y 4  is selected from C, N, NH, N-alkyl, O, or S; 
       R 3  and R 5  are each a substituent on any one or more ring atoms independently selected from H, a halogen, Cl, F, Br, NO 2 , CH 3 , CH 3 CH 2 , or higher or lower substituted or unsubstituted straight chain or branched aliphatic; 
       Z is an amide, amine, imine, urea, thiourea, or thioamide functional group (either constitutional isomer, where possible); and 
       n=0, 1, 2, or 3; 
       where X 1  and X 2  are not both N-alkyl, O, S, or O and S together, N-alkyl and O together, or N-Alkyl and S together. 
     
   
   
       13 . A composition as in  claim 12 , wherein the compound is present in a therapeutically effective amount for enhancing production of BRCA1. 
   
   
       14 . A method of in treating, inhibiting, and/or preventing breast and/or ovarian cancer, said method comprising:
 providing a compound as in  claim 1 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production.   
   
   
       15 . A method as in  claim 14 , wherein the increased BRCA1 production is sufficient to inhibit the growth and/or propagation of breast and/or ovarian cancer cells. 
   
   
       16 . A method as in  claim 14 , wherein the increased BRCA1 production is increased compared to BRCA1 production in the subject prior to being administered the compound. 
   
   
       17 . A method of in treating, inhibiting, and/or preventing breast and/or ovarian cancer, said method comprising:
 providing a compound as in  claim 6 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production.   
   
   
       18 . A method of in treating, inhibiting, and/or preventing breast and/or ovarian cancer, said method comprising:
 providing a compound as in  claim 8 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production.   
   
   
       19 . A method of in treating, inhibiting, and/or preventing breast and/or ovarian cancer, said method comprising:
 providing a compound as in  claim 10 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production.   
   
   
       20 . A method of in treating, inhibiting, and/or preventing breast and/or ovarian cancer, said method comprising:
 providing a compound as in  claim 12 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production.   
   
   
       21 . A method of increasing BRCA1 production in breast and/or ovarian cancer cells, said method comprising:
 providing a compound as in  claim 1 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production from a low level of the BRCA1 production in the breast and/or ovarian cancer cells.   
   
   
       22 . A method as in  claim 21 , wherein the increased BRCA1 production is sufficient to inhibit the growth of the breast and/or ovarian cancer cells. 
   
   
       23 . A method of increasing BRCA1 production in breast and/or ovarian cancer cells, said method comprising:
 providing a compound as in  claim 6 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production from a low level of the BRCA1 production in the breast and/or ovarian cancer cells.   
   
   
       24 . A method of increasing BRCA1 production in breast and/or ovarian cancer cells, said method comprising:
 providing a compound as in  claim 8 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production from a low level of the BRCA1 production in the breast and/or ovarian cancer cells.   
   
   
       25 . A method of increasing BRCA1 production in breast and/or ovarian cancer cells, said method comprising:
 providing a compound as in  claim 10 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production from a low level of the BRCA1 production in the breast and/or ovarian cancer cells.   
   
   
       26 . A method of increasing BRCA1 production in breast and/or ovarian cancer cells, said method comprising:
 providing a compound as in  claim 12 ; and   administering a therapeutically effective amount of the compound to a subject so as to increase BRCA1 production from a low level of the BRCA1 production in the breast and/or ovarian cancer cells.   
   
   
       27 . A cancerous breast or ovarian cell comprising a therapeutically effective amount of a compound having a compound as in  claim 1  so as to induce or increase BRCA1 production in the cell. 
   
   
       28 . A cell as in  claim 27 , wherein the BRCA1 production is increased from a low level of the BRCA1 production in the cell. 
   
   
       29 . A cancerous breast or ovarian cell comprising a therapeutically effective amount of a compound as in  claim 6  so as to induce or increase BRCA1 production in the cell. 
   
   
       30 . A cancerous breast or ovarian cell comprising a therapeutically effective amount of a compound having a compound as in  claim 8  so as to induce or increase BRCA1 production in the cell. 
   
   
       31 . A cancerous breast or ovarian cell comprising a therapeutically effective amount of a compound having a compound as in  claim 10  so as to induce or increase BRCA1 production in the cell. 
   
   
       32 . A cancerous breast or ovarian cell comprising a therapeutically effective amount of a compound having a compound as in  claim 12  so as to induce or increase BRCA1 production in the cell.