Substrate-Selective Enzyme Inhibitors

Trends Pharmacol Sci. 2019 Oct;40(10):716-718. doi: 10.1016/ Epub 2019 Aug 2.


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.

Keywords: chemical biology; enzyme reprogramming; exo site; insulin-degrading enzyme; substrate-selective inhibition.

Publication types

  • Comment

MeSH terms

  • Enzyme Inhibitors
  • Insulin
  • Insulysin*


  • Enzyme Inhibitors
  • Insulin
  • Insulysin