Mgmt inhibitor combinations for the treatment of neoplastic disorders

Abstract

A method of treating a neoplastic disease in a subject includes administering to neoplastic cells of the subject an MGMT inhibitor and at least one of an antimitotic agent or a DNA damaging agent.

1 - 16 . (canceled) 
     
     
         17 . A pharmaceutical composition for treating a a cancer resistant to treatment with an anti-mitotic agent comprising:
 at least on taxane and at least one MGMT inhibitor at an amount effective to potentiate the effect of the taxane at promoting mitotic cell death of the cancer, wherein the at least one MGMT inhibitor is selected from the group consisting of O 6 -benzylguanine (BG), O 6 -2-fluoropyridinylmethyl guanine (FPG), O 6 -3-iodobenzyl guanine, O 6 -4-bromothenylguanine (PaTrin-2, UK), and O 6 -5-iodothenylguanine , O 6 -benzyl-8-oxoguanine (MW 257), O 6 -(p-chlorobenzyl)guanine, O 6 -(p-methylbenzyl)guanine (MW255), O 6 -(p-bromobenzyl)guanine (MW 320), O 6 -(p-isopropylbenzyl)guanine (MW 283), O 6 -(3,5-dimethylbenzyl)guanine (MW 269), O 6 -(p-n-butylbenzyl)guanine (MW 297), O 6 -(p-hydroxymethybenzyl)guanine (MW271), O 6 -benzylhypoxanthine, N 2 -acetyl-O 6 -benzylguanine (MW 283), N 2 -acetyl-O 6 -benzyl-8-oxo-guanine (MW 299), 2-amino-6-(p-methy-benzyl-thio)purine, 2-amino-6-(benzyloxy)-9-[(ethoxycarbonyl)methyl]purine, 2-amino-6-(benzyloxy)-9-(pivaloyloxymethyl)purine, 2-amino-6-(benzyl-thio)purine, O6-benzyl-7,8-dihydro-8-oxoguanine (8-oxo-BG), 2,4,5-triamino-6-benzyloxyprimidine (5-amino-BP), O6-benzyl-9[(3-oxo-5α-androstan-17β-yloxycarbonyl)methyl]guanine (DHT-BG), O6-benzyl-9-[(3-oxo-4-androsten-17↑-yloxvcarbonyl)methyl(guanine (AND-BG), 8-amino-O6-benzylguanine (8-amino-BG), C8-linker-glucose-conjugates thereof, 2,4-diamino-6 benzyloxy-5-nitrosopyrimidine (5-nitroso-BP) and 2,4-diamino-6-benzyloxy-5-nitropyrimidine (5-nitro-BP), 2-amino-4-benzyloxy-5-nitropyrimidine, and combinations thereof.   
     
     
         18 . The pharmaceutical composition of  claim 17 , the taxane being an antimitotic agent selected from the group consisting of paclitaxel, docetaxel, and combinations thereof. 
     
     
         19 . (canceled) 
     
     
         20 . The pharmaceutical composition of  claim 17 , further comprising a DNA damaging agent. 
     
     
         21 . The pharmaceutical composition of  claim 20 , the DNA damaging agent comprising an alkylating agent. 
     
     
         22 . The pharmaceutical composition of  claim 17 , the MG MT inhibitor comprising O 6 -benzylguanine (BG). 
     
     
         23 . The pharmaceutical composition of  claim 17 , being provided as an intravenous formulation.