New Light on the “Old” Chloride Channel Blocker DIDS

4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) has been used as an inhibitor of anion transporters and channels since the early 1970s. A study in this issue shows that DIDS hydrolyzes in aqueous solution and then multimerizes to di-, tri-, tetra-, and pentameric polythioureas, which inhibit both the bacterial ClC-ec1 Cl(-)/H(+) exchanger and the mammalian ClC-Ka chloride channel 3-200 times more potently than DIDS itself. The DIDS tetra- and pentamer could potentially act as tethered blockers that simultaneously obstruct both chloride pathways in the dimeric CLC proteins.