SLC22A11 Inhibitors

Chemical inhibitors of SLC22A11 employ distinct mechanisms to impede the protein's ability to transport organic anions across cellular membranes. Probenecid, for example, inhibits SLC22A11 by competitively binding to the substrate recognition sites of the transporter, which obstructs the passage of endogenous and exogenous anions that are normally carried by this protein. Similarly, Benzbromarone hinders the activity of SLC22A11 by rivalling the substrates for the same transport sites, leading to a diminished transport activity of the protein. This mode of competitive inhibition is also how Indomethacin operates; it binds to the substrate sites on SLC22A11, disrupting its normal function. Ibuprofen and Ketoprofen inhibit SLC22A11 by competing with its natural substrates, thus reducing the protein's efficiency in transporting anionic compounds. Losartan acts as an inhibitor of SLC22A11 by competing for anion transport sites, which blocks other substrates from binding and being translocated by the protein. In a like manner, Cimetidine's inhibition of SLC22A11 arises from its ability to compete with the transporter's substrates, effectively preventing the protein from performing its transport duties. Phenylbutazone impedes SLC22A11 by binding to the protein and precluding the movement of physiological substrates, serving as a competitive inhibitor. Atorvastatin and Rosuvastatin, both statin drugs, obstruct SLC22A11 by occupying the binding sites on the transporter, which prevents the physiological interactions required for the protein's normal function. Diclofenac and Furosemide also obstruct SLC22A11, with Diclofenac binding preferentially to the transporter, thus blocking normal substrate movement, and Furosemide competing with physiological anions for the binding sites, which hampers the protein's ability to transport these molecules across the membrane.