Novel natural and synthetic inhibitors of solute carriers SGLT1 and SGLT2.

ABSTRACT: Selective analogs of the natural glycoside phloridzin are marketed drugs that reduce hyperglycemia in diabetes by inhibiting the active sodium glucose cotransporter SGLT2 in the kidneys. In addition, intestinal SGLT1 is now recognized as a target for glycemic control. To expand available type 2 diabetes remedies, we aimed to find novel SGLT1 inhibitors beyond the chemical space of glycosides. We screened a bioactive compound library for SGLT1 inhibitors and tested primary hits and additional structurally similar molecules on SGLT1 and SGLT2 (SGLT1/2). Novel SGLT1/2 inhibitors were discovered in separate chemical clusters of natural and synthetic compounds. These have IC₅₀-values in the 10-100 μmol/L range. The most potent identified novel inhibitors from different chemical clust

SUBMITTER: Oranje P 

PROVIDER: S-EPMC6664820 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature