The Salk Institute for Biological Studies, Clayton Foundation Laboratories for Peptide Biology, 10010 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
The Salk Institute for Biological Studies, Clayton Foundation Laboratories for Peptide Biology, 10010 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Trends Pharmacol Sci. 2019 Oct;40(10):716-718. doi: 10.1016/j.tips.2019.07.009. 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.
具有多种底物的酶对药物开发提出了独特的挑战，因为它们增加了针对目标的副作用的可能性。Maianti 及其同事（《自然-化学生物学》，2019 年）确定了具有改变胰岛素降解酶（IDE）底物选择性能力的新型外位抑制剂。他们的工作为发现小分子酶抑制剂开辟了新的治疗途径，并重新定义了我们目前对多底物酶药物的理解。
