Inhibitors of multidrug resistance (MDR) have affinity for MDR substrates.
Multidrug-resistance (MDR) occurs in many bacterial species and tumour cells. MDR functions by membrane proteins which export drugs from cells, resulting in a low ineffective concentration of the drug. We have shown by molecular modelling that inhibitors of MDR have affinity for substrates of MDR transporters. This affinity may facilitate drug entry into cells and a large inhibitor-drug complex may be a poorer substrate for the MDR mechanism. This complex would effectively 'cloak' the drug rendering it unavailable for efflux.
Zloh
Mire
M
Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK. mire.zloh@ulsop.ac.uk
Kaatz
Glenn W
GW
Gibbons
Simon
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D008024:Ligands; D008958:Models, Molecular
D018435:ATP Binding Cassette Transporter, Subfamily B; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D008024:Ligands