Inhibiting Gram-Negative RND Pumps

Based on the elucidation of the structure and the efflux mechanism of RND transporters, there may be several potential ways to interfere with their function. 

Inhibitors could target the substrate binding pocket. This voluminous pocket can accommodate an extraordinary variety of structures hence, many distinct pharmacophore classes can be foreseen. Importantly, the binding site ofthe RND transporter is located in the periplasm, so that an inhibitor need only cross one membrane. 

EPis with seiective activity against the MexAB-OprM compiex from P. aeruginosa. These inhibitors might interact with the transporter at the aiiosteric moduiator site, (c) EPis with activity against transporters from various species of Enterobacteriaceae. Their mode of action is mostiy uncharacterized. 

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