Treatment of cancer and other conditions using a transcription factor modulator

Abstract

The present disclosure provides novel methods for treating cancer and conditions regulatable by a transcription factor and/or cofactor using specific compounds, as well as compositions, and pharmaceutical formulations. In certain embodiments, the compounds are transcription factor modulators.

What is claimed is: 
     
         1 . A method of treating a cancer or a tumor in a subject comprising administering to the subject a therapeutically effective amount of one or more compounds or a composition or pharmaceutical formulation thereof, wherein the one or more compounds comprise a structure selected from the group consisting of YT54, Structure I, Structure II, Structure IIIA, Structure IIIB, Structure IIIC, Structure IVA, Structure IVB, Structure IVC, Structure IVD, Structure VA, Structure VB, Structure VC, Structure VD, Structure VE, Structure VI, Structure VIIA, Structure VIIB, Structure VIIC, Structure VIID, Structure VIIE, and Structure VIII, including pharmaceutically acceptable solvates, pharmaceutically acceptable prodrugs, pharmaceutically acceptable salts and pharmaceutically acceptable stereoisomers thereof, wherein:
 A and B rings are each independently selected from the group consisting of phenyl, pyridyl and N-alkylated pyridyl rings;   R 1 -R 5  are each independently selected from the group consisting of hydrogen, halogen, alkyl, and haloalkyl, wherein at least one or two of R 1 -R 5  are halogen and/or haloalkyl;   R 6  and R 7  are an alkyl group having 1-3 carbon atoms;   X 1  and X 2  are independently selected from —NHC(═O)— or —C(═O)—NH—; and   L 1  is —(CH 2 ) n —, where n is 4, 5, 6, 7, or 8, where one or more —CH 2 — moieties are optionally replaced with one or more substituents selected from the group consisting of —O—, —S—, —C(═O)—, —S(═O)—, —S(═O) 2 —, —NH—C(═O)—, —C(═O)—NH—, —NR—, —C═C—, carbon-carbon triple bond, phenylene, 1,4-phenylene and cyclohexylene, 1,4-cyclohexylene, wherein R is hydrogen, alkyl or aryl.   
     
     
         2 . The method according to  claim 1 , wherein L 1  is —(CH 2 ) n —, where n is 4, 5, 6, 7, or 8. 
     
     
         3 . The method according to  claim 2 , wherein:
 R 3  and R 4  are halogen; and   R 1 , R 2 , and R 5  are hydrogen.   
     
     
         4 . The method according to  claim 3 , wherein the halogen is bromine. 
     
     
         5 . The method according to  claim 2 , wherein the cancer or tumor is selected from the group consisting of breast cancer, central nervous system cancer, colon cancer, prostate cancer, lung cancer, leukemia, renal cancer, ovarian cancer, melanoma, liver cancer, and cervical cancer. 
     
     
         6 . The method according to  claim 4 , wherein the cancer or tumor is selected from the group consisting of breast cancer, central nervous system cancer, colon cancer, prostate cancer, lung cancer, leukemia, renal cancer, ovarian cancer, melanoma, liver cancer, and cervical cancer. 
     
     
         7 . The method according to  claim 2 , wherein the cancer treated is leukemia selected from the group consisting of acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), CML (imatinib resistant), multiple myeloma, B-cell myelomonocytic leukemia, T-cell myelomonocytic leukemia, biphenotypic B-cell leukemia, and/or lymphoma. 
     
     
         8 . The method according to  claim 4 , wherein the cancer treated is leukemia selected from the group consisting of acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), CML (imatinib resistant), multiple myeloma, B-cell myelomonocytic leukemia, T-cell myelomonocytic leukemia, biphenotypic B-cell leukemia, and/or lymphoma. 
     
     
         9 . The method according to  claim 7 , wherein the one or more compounds are selected from the group consisting of YT29, YT30, YT53, YT54, YT61, YT65, YT67, YT68, YT73, YT74, and YT139, or pharmaceutically acceptable solvates, pharmaceutically acceptable prodrugs, pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof. 
     
     
         10 . The method according to  claim 7 , wherein the leukemia is resistant to Imatinib or Gleevec. 
     
     
         11 . The method according to  claim 7 , wherein the leukemia has a p53 mutation in the genome of the leukemia cells. 
     
     
         12 . The method according to  claim 7 , wherein the leukemia has wild type p53 in the genome of the leukemia cells. 
     
     
         13 . The method according to  claim 7 , wherein the leukemia has a Multidrug Resistance value between 1 and 50. 
     
     
         14 . The method according to  claim 7 , wherein the leukemia has a Multidrug Resistance value between −15 and 0. 
     
     
         15 . The method according to  claim 2 , wherein the one or more compounds or a composition or pharmaceutical formulation thereof may be administered orally or by intraperitoneal injection. 
     
     
         16 . The method according to  claim 2 , wherein the one or more compounds or a composition or pharmaceutical formulation thereof may be administered in combination with a pharmaceutically effective amount of imatinib. 
     
     
         17 . A method of treating cancer or a tumor in a subject comprising administering to the subject a therapeutically effective amount of one or more compounds or a composition or pharmaceutical formulation thereof, wherein the one or more compounds comprise a structure selected from the group consisting of YT45, T46, YT51, YT58, YT62˜YT63, YT76˜YT80, YT86, YT88, YT91, YT99, YT108˜YT110, YT116˜YT118, YT121˜YT123, YT127, YT128, YT131, YT134˜YT136, and 137-139 including pharmaceutically acceptable solvates, pharmaceutically acceptable prodrugs, pharmaceutically acceptable salts and pharmaceutically acceptable stereoisomers thereof. 
     
     
         18 . The method of  claim 17 , wherein the cancer is leukemia selected from the group consisting of acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), CML (imatinib resistant), multiple myeloma, B-cell myelomonocytic leukemia, T-cell myelomonocytic leukemia, biphenotypic B-cell leukemia, and/or lymphoma. 
     
     
         19 . The method of  claim 18 , wherein the one or more compounds or a composition or pharmaceutical formulation thereof may be administered in combination with a pharmaceutically effective amount of Imatinib or one or more compounds of  claim 1 . 
     
     
         20 . The method of  claim 18 , wherein the one or more compounds or a composition or pharmaceutical formulation thereof may be administered orally or by intraperitoneal injection.