Inhibitors of Multidrug Efflux Transporters: Their Membrane and Protein Interactions

Modulators and inhibitors of multidrug efflux transporters, like P-glycoprotein, are used to reduce or inhibit multidrug resistance, MDR, which leads to a failure of the chemotherapy of e.g. cancers, epilepsy, bacterial, parasitic, and fungal diseases. Binding and transport of first-, second-, and third-generation modulators and inhibitors of P-glycoprotein are discussed, taking into account the properties of the drug (Hbonding potential, dimensions, and pKα values) as well as the properties of the membrane. Keywords: p-glycoprotein, first, second, and third-generation inhibitors, modulators, membrane partitioning, transporter binding, transport kinetics