Kinase protein binding inhibitors

Abstract

The invention provides compounds capable of treating a subject suffering from or being susceptible to a cell proliferative disorder (especially, cancer), methods of identifying and using the compounds, pharmaceutical compositions and kits thereof.

1 - 12 . (canceled) 
     
     
         13 . A method of treating a subject suffering from or susceptible to cancer, said method comprising administering to said subject thereof an effective amount of a compound selected from the group consisting of
 a) 2-(hydroxymethyl)-6-imino-2,3,3a,9a-tetrahydro-6H-furo[2,3:4,5][1,3]oxazolo[3,2-a]pyrimidin-3-yl dihydrogen phosphate;   b) 4-(methylthio)-7-(5-O-phosphono-D-ribofuranosyl)-{7H-Pyrrolo[2,3-d]pyrimidine}; c) 1,1′-(1,7,9-Trihydroxy-8,9b-dimethyl-3-oxo-4-a-(phenylthio)-3,4,4a,9b-tetrahydrodibenzo-[b,d]furan-2,6-diyl)diethanone;   d) 3-Methyl-2,4-disulfopentanedioic acid; and   e) 1-Aminopropane-1,3-diyldiphosphonic acid;   or a pharmaceutically acceptable salt thereof.   
     
     
         14 . The method of  claim 13 , wherein said compound is 4-(methylthio)-7-(5-O-phosphono-D-ribofuranosyl)-{7H-Pyrrolo[2,3-d]pyrimidine}, or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 13 , wherein said cancer is pancreatic cancer, melanoma cancer, or esophageal cancer. 
     
     
         16 . The method of  claim 13 , wherein said method further comprises administering to said subject an additional therapeutic agent. 
     
     
         17 . The method of  claim 13 , wherein said method further comprises treating said subject thereof with surgery, chemotherapy, radiation, immunotherapy, monoclonal antibody therapy or epidermal growth factor receptor therapies. 
     
     
         18 - 33 . (canceled) 
     
     
         34 . A kit for use in treating a subject suffering from or susceptible to a cell proliferative disorder, said kit comprising an effective amount of a compound capable of modulating binding interactions between FAK and IGF-1R. 
     
     
         35 . The kit of  claim 34 , wherein said compound is selected from the group consisting of
 a) 2-(Hydroxymethyl)-6-imino-2,3,3a,9a-tetrahydro-6H-furo[2,3:4,5][1,3]oxazolo[3,2-a]pyrimidin-3-yl dihydrogen phosphate;   b) 4-(Methylthio)-7-(5-O-phosphono-D-ribofuranosyl)-{7H-Pyrrolo[2,3-d]pyrimidine}; c) 1,1′-(1,7,9-Trihydroxy-8,9b-dimethyl-3-oxo-4-a-(phenylthio)-3,4,4a,9b-tetrahydrodibenzo-[b,d]furan-2,6-diyl)diethanone;   d) 3-Methyl-2,4-disulfopentanedioic acid; and   e) 1-Aminopropane-1,3-diyldiphosphonic acid;   or a pharmaceutically acceptable salt thereof.   
     
     
         36 . The kit of  claim 35 , wherein said compound is 4-(methylthio)-7-(5-O-phosphono-D-ribofuranosyl)-{7H-Pyrrolo[2,3-d]pyrimidine} or a pharmaceutically acceptable salt thereof. 
     
     
         37 . The kit of  claim 34 , wherein said cell proliferative disorder is a cancer. 
     
     
         38 . The kit of  claim 37 , wherein said cancer is a cancer of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid or a distant metastasis of a solid tumor. 
     
     
         39 . The kit of  claim 38 , wherein said cancer is pancreatic cancer, melanoma cancer, or esophageal cancer. 
     
     
         40 . The kit of  claim 39 , wherein said cancer is pancreatic cancer. 
     
     
         41 . The kit of  claim 34 , further comprising an additional therapeutic agent. 
     
     
         42 . The kit of  claim 41 , wherein said additional therapeutic agent is selected from the group consisting of asparaginase, bleomycin, calcein-AM, carboplatin, carmustine, chlorambucil, cisplatin, colaspase, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin (adriamycine), epirubicin, etoposide, ET-743, erlotinib, 5-fluorouracil, gemcitabine, gefitinib, hexamethylmelamine, hydroxyurea, ifosfamide, irinotecan, leucovorin, lomustine, mechlorethamine, 6-mercaptopurine, mesna, methotrexate, mitomycin C, mitoxantrone, NVP-AEW541, paclitaxel, prednisolone, prednisone, procarbazine, raloxifen, rhodamine-123, streptozocin, TAE226, tamoxifen, thioguanine, topotecan, vinblastine, vincristine, vindesine, and zalypsis. 
     
     
         43 . A pharmaceutical composition for treating a subject suffering from or susceptible to cancer, said composition comprising an effective amount of a compound capable of modulating binding interactions between FAK and IGF-1R, and a pharmaceutically acceptable carrier or diluent. 
     
     
         44 . The pharmaceutical composition of  claim 43 , wherein said compound is selected from the group consisting of
 a) 2-(Hydroxymethyl)-6-imino-2,3,3a,9a-tetrahydro-6H-furo[2,3:4,5][1,3]oxazolo[3,2-a]pyrimidin-3-yl dihydrogen phosphate;   b) 4-(Methylthio)-7-(5-O-phosphono-D-ribofuranosyl)-{7H-Pyrrolo[2,3-d]pyrimidine}; c) 1,1′-(1,7,9-Trihydroxy-8,9b-dimethyl-3-oxo-4-a-(phenylthio)-3,4,4a,9b-tetrahydrodibenzo-[b,d]furan-2,6-diyl)diethanone;   d) 3-Methyl-2,4-disulfopentanedioic acid; and   e) 1-Aminopropane-1,3-diyldiphosphonic acid;   or a pharmaceutically acceptable salt thereof.   
     
     
         45 . The pharmaceutical composition of  claim 44 , wherein said compound is 4-(methylthio)-7-(5-O-phosphono-D-ribofuranosyl)-{7H-Pyrrolo[2,3-d]pyrimidine} or a pharmaceutically acceptable salt thereof. 
     
     
         46 . The pharmaceutical composition of  claim 43 , wherein said cancer is pancreatic cancer, melanoma cancer, or esophageal cancer.