Substrate-selective small-molecule modulators of enzymes: Mechanisms and opportunities.
Substrate-selective small-molecule modulators of enzymes: Mechanisms and opportunities.
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DOI：
10.1016/j.cbpa.2022.102231
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发表时间：
2022-11
影响因子：
7.8
通讯作者：
Hening Lin
中科院分区：
文献类型：
--
作者：
Hening Lin
Small-molecule inhibitors of enzymes are widely used tools in reverse chemical genetics to probe biology and explore therapeutic opportunities. They are often compared with genetic knockdown or knockout and are expected to produce phenotypes similar to the genetic perturbations. This review aims to highlight that small molecule inhibitors of enzymes and genetic perturbations may not necessarily produce the same phenotype due to the possibility of substrate-selective or substrate-dependent effects of the inhibitors. Examples of substrate-selective inhibitors and the mechanisms for the substrate-selective effects are discussed. Substrate-selective modulators of enzymes have distinct advantages and cannot be easily replaced with biologics. Thus, they present an exciting opportunity for chemical biologists and medicinal chemists.
