Lu Kuan-Yi
Duke University, Department of Chemistry 5324 FFSC, 124 Science Drive, Durham, NC, 27708, USA.
Chembiochem. 2020 Nov 16;21(22):3189-3191. doi: 10.1002/cbic.202000439. Epub 2020 Sep 16.
Illuminating drugs' mechanisms of action and their effects on the biomolecules of pathogens and humans is a much-needed next step to facilitate pharmaceutical development. Although studies have linked some drugs to their therapeutic targets by using transcriptomics and genomics, these approaches have intrinsic limitations and cannot directly assess drugs' effects on their protein targets. In this regard, chemoproteomic methods can detect protein-ligand interactions and quantitate the chemical or thermal stability changes of the entire detectible proteomes induced by drugs of interest. These widely applicable techniques have recently been adapted to deconvolute the mechanisms of action of antiparasitic drugs and successfully identified an essential target that was previously not known to be druggable. A continued effort to Integrate chemoproteomics into the drug-development pipeline could greatly improve our understanding of drugs' mechanisms, toxicity and pharmacodynamic properties.
阐明药物的作用机制及其对病原体和人体生物分子的影响是促进药物研发急需的下一步。尽管研究已通过转录组学和基因组学将一些药物与其治疗靶点联系起来，但这些方法存在固有局限性，无法直接评估药物对其蛋白质靶点的影响。在这方面，化学蛋白质组学方法可以检测蛋白质-配体相互作用，并定量由感兴趣的药物诱导的整个可检测蛋白质组的化学或热稳定性变化。这些广泛应用的技术最近已被用于剖析抗寄生虫药物的作用机制，并成功鉴定出一个以前未知可成药的关键靶点。持续努力将化学蛋白质组学整合到药物研发流程中，有望极大地增进我们对药物作用机制、毒性和药效学特性的理解。
