Estimation of the chemosensitizing activity of modulators of multi-drug resistance via combined simultaneous analysis of sigmoidal dose-response curves.
The potency of modulators which re-establish sensitivity of resistant tumour cells to cytotoxic drugs is not usually described by ED50 values, even though such values are needed for comparison of modulator activity. Various methods are reported for the determination of ED50 values of propafenone-type modulators of multi-drug resistance in cytotoxicity assays. Best results were obtained by using a combined simultaneous analysis of dose-response curve families. This approach enables calculation of statistically highly significant ED50 values without any data reduction directly from the original data points obtained in daunomycin cytotoxicity assays. The method also enables extrapolation of the ED50 values of compounds with low activity or poor solubility, or both.
Ecker
G
G
Institute of Pharmaceutical Chemistry, University of Vienna, Wien, Austria.
Chiba
P
P
Schaper
K J
KJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D011405:Propafenone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D011405:Propafenone; C022616:thiazolyl blue; D003630:Daunorubicin