Patent ID: 8445271

Claim:
A process for determining drug resistance of cells of interest, said process comprising the steps of: (A) providing: (i) a clinical or biological sample comprising cells; (ii) at least one xanthene compound that is transportable across a cell membrane by membrane transporters multidrug resistance 1 (MDR1), multidrug resistance associated protein 1 (MRP) and breast cancer resistant protein (BCRP); and (iii) one or more membrane transporter inhibitors; (B) contacting cells from a first portion of said clinical or biological sample with said at least one xanthene compound; (C) contacting cells from a second portion of said clinical or biological sample (i) with said at least one xanthene compound and said one or more inhibitors; (D) measuring fluorescent signals generated in step (B) and step (C); and (E) comparing the fluorescent signals measured in step (D) to determine elevated activities of said MDR1, MRP and BCRP, or a combination thereof, thereby determining the drug resistance of said cells of interest, wherein said at least one xanthene compound has the structure wherein R 1 -R 6 are independently H, halogen, carboxy, alkoxy, aryloxy, thiol, alkylthiol, arylthiol, azido, nitro, nitroso, cyano, amino, hydroxy, phosphonyl, sulfonyl, carbonyl, boronic acid, aryl, or heteroaryl; or alkyl, or alkoxy, optionally substituted one or more times by halogen, amino, hydroxy, phosphonyl, sulfonyl, carbonyl, boronic acid, aryl or heteroaryl, heteroatom Y is independently selected from O, S, Se, NR 9 and CR. 10 R 11 , X is independently selected from OR 12 , NR 12 R 13 and Z is independently selected from O and NR 16 R 17 , where each R 9 , R 10 , R 11 , R 12 , R 13 , R 16 and R 17 is independently H, an alkyl having 1-12 carbons, carboxyalkyl, substituted or non-substituted amino alkyl or alkylsulfonate, T and U are independently hydrogen, alkyl having 1-12 carbons, alkoxy having 1-12 carbons, aryloxy, amino, halogen, cyano, carboxy, carboxyalkyl, acetoxymethylcarbonyl, carbonyl, sulfonyl, phosphonyl, boronic acid, aryl, and heteroaryl, and V and W are independently selected from OR 14 , SR 15 or NR 12 R 13 , such that at least one of V or W, in combination with NR 7 R 8 , forms a metal chelator, where each R 7 , R 8 , and R 12 -R 15 are independently H, an alkyl having 1-12 carbons, carboxyalkyl, alkoxy or aryloxy.