SLC26A8 Inhibitors

Chemical inhibitors of SLC26A8 can influence its activity through various mechanisms that directly affect the protein's anion transport capability. DIDS and NPPB are known to inhibit SLC26A8 by directly binding to the protein, which can lead to the prevention of anion exchange across the membrane. This binding can obstruct the channels through which anions such as chloride and bicarbonate typically flow, thus impeding the essential transport function of SLC26A8. Similarly, GlyH-101 targets the anion conductance directly, preventing the movement of these ions through SLC26A8, which is crucial for its function in anion transport and exchange.

Moreover, CFTR(inh)-172 and PPQ-102 inhibit SLC26A8 by interacting with the CFTR protein, which is thought to form functional complexes with SLC26A8. These inhibitors can reduce the activity of CFTR, which in turn can decrease the associated activity of SLC26A8, demonstrating a method of indirect inhibition through protein-protein interaction. DCPIB, although a selective inhibitor of volume-regulated anion channels, can also diminish the transport capacity of SLC26A8 by altering the function of channels that may interact with SLC26A8. Tannic acid, through protein precipitation, can alter the conformation or mask active sites of SLC26A8, leading to reduced transport activity. This illustrates how changes in the protein's tertiary structure or the availability of functional groups essential for activity can result in inhibition. Flufenamic acid, mefenamic acid, and niflumic acid can inhibit SLC26A8 by changing the anion transport dynamics, which could involve alterations in the membrane environment or the protein conformation necessary for SLC26A8's function. Indanyloxyacetic acid and diphenylamine-2-carboxylate function by targeting chloride channels and transporters, which can compete with the anions that SLC26A8 transports, thereby blocking the substrate's path through the channel and effectively inhibiting the protein's activity.