Compounds For Reducing Drug Resistance And Uses Thereof

Abstract

This invention provides compounds capable of reducing drug resistance in a subject undergoing cancer treatment, methods using the compounds, compositions, and methods for identifying such compounds.

1 . A method of reducing drug resistance in a subject undergoing cancer treatment, said method comprising administering to a subject in need thereof an effective amount of (2-(4-Methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol or a pharmaceutically acceptable salt thereof, thereby reducing drug resistance in said subject. 
     
     
         2 . The method of  claim 1  , wherein (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin- 2-yl)methanol or a pharmaceutically acceptable salt thereof is administered at a dose that is lower than the dose required to produce cytotoxicity in said subject. 
     
     
         3 . The method of  claim 2 , wherein (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin- 2-yl)methanol or a pharmaceutically acceptable salt thereof is administered to said subject at a dose at least 10 fold lower than that required to produce cytotoxicity in said subject. 
     
     
         4 . The method of  claim 3 , wherein (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin- 2-yl)methanol or its pharmaceutically acceptable salt thereof is administered to said subject at a dose at least 50 fold lower than that required to produce cytotoxicity in said subject. 
     
     
         5 . The method of  claim 1  , wherein (2-(4-methoxyphenyl)quino lin-4-yl)(piperidin- 2-yl)methanol or a pharmaceutically acceptable salt thereof is administered to said subject at a dose between about 0.001 mg/Kg and about 100 mg/Kg. 
     
     
         6 . The method of  claim 1  , further comprising administering to said subject an anticancer therapeutic agent. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . The method of  claim 6 , wherein (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin- 2-yl)methanol or a pharmaceutically acceptable salt thereof is administered to said subject after the administration of said anti-cancer therapeutic agent. 
     
     
         10 . The method of  claim 6 , wherein said anti-cancer 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, 5-fluorouracil, gemcitabine, hexamethylmelamine, hydroxyurea, ifosfamide, irinotecan, leucovorin, lomustine, mechlorethamine, 6-mercaptopurine, mesna, methotrexate, mitomycin C, mitoxantrone, paclitaxel, prednisolone, prednisone, procarbazine, raloxifen, rhodamine-123, streptozocin, tamoxifen, thioguanine, topotecan, vinblastine, vincristine, vindesine, and zalypsis. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The method of  claim 1  , wherein said cancer treatment is for a cancer of 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. 
     
     
         14 - 18 . (canceled) 
     
     
         19 . A method for treating cancer in a subject, said method comprising a) identifying a subject undergoing cancer treatment and having developed or being susceptible to develop drug resistance; b) administering to said subject an effective amount of (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol or a pharmaceutically acceptable salt thereof, wherein said effective amount is sufficient to reduce drug resistance in said subject, thereby treating cancer in a subject. 
     
     
         20 . The method of  claim 19 , wherein said method further comprises discontinuing said cancer treatment. 
     
     
         21 . The method of  claim 20 , wherein said cancer treatment is discontinued prior to the administration of (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 20 , wherein said cancer treatment is discontinued after the administration of (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The method of  claim 20 , wherein said method further comprises administering to said subject a subsequent cancer treatment after the discontinuation of said cancer treatment and the administration of (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol or a pharmaceutically acceptable salt thereof. 
     
     
         24 . The method of  claim 23 , wherein said subsequent cancer treatment is the same as said discontinued cancer treatment. 
     
     
         25 . The method of  claim 23 , wherein said subsequent cancer treatment is different from said discontinued cancer treatment. 
     
     
         26 . The method of  claim 23 , further comprising administering to said subject an additional effective amount of (2-(4-methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol or a pharmaceutically acceptable salt thereof after administration of said subsequent cancer treatment. 
     
     
         27 - 34 . (canceled) 
     
     
         35 . A method of identifying a compound to reduce drug resistance in a cancer treatment, said method comprising a) screening compounds for their inhibitory activities on drug resistant cells line through high-throughput assay; b) identifying a lead compound; and c) evaluating the ability of said lead compound to inhibit or modulate the function of P-glycoprotein (Pgp). 
     
     
         36 . The method of  claim 35  further comprising evaluating the ability of said lead compound to inhibit MRP1 function. 
     
     
         37 . The method of  claim 35  further comprising evaluating the ability of said lead compound to affect BCRP mediated drug resistance.