Reversers of the multidrug resistance transporter P-glycoprotein

Multidrug resistance can arise from the presence of the membrane-bound pump, P-glycoprotein, in a tumor. Major efforts have been made to develop inhibitors of this pump, and a number of promising blockers have reached late stages of clinical trials. The kinetics of the inhibition of P-glycoprotein is complex, with numerous binding sites that can interact synergistically. Reversers of increased affinity and specificity could, in principle, be developed on the basis of these synergies, and offer some promise in cancer therapeutics.