Abstract
Enzymes with multiple substrates pose a unique challenge for drug development because of an increased potential for on-target side effects. Maianti and colleagues (Nat. Chem. Biol., 2019) identify novel exo-site inhibitors with abilities to alter the substrate-selectivity of insulin-degrading enzymes (IDE). Their work illuminates new therapeutic avenues for discovering small-molecule enzyme inhibitors and redefines our current understanding of drugging enzymes with multiple substrates.
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