Hopkins Andrew L, Mason Jonathan S, Overington John P
Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK.
Curr Opin Struct Biol. 2006 Feb;16(1):127-36. doi: 10.1016/j.sbi.2006.01.013. Epub 2006 Jan 25.
Structure-based drug design is now used widely in modern medicinal chemistry. The application of structural biology to medicinal chemistry has heralded the "rational drug design" vision of discovering exquisitely selective ligands. However, recent advances in post-genomic biology are indicating that polypharmacology may be a necessary trait for the efficacy of many drugs, therefore questioning the "one drug, one target" assumption of current rational drug design. By combining advances in chemoinformatics and structural biology, it might be possible to rationally design the next generation of promiscuous drugs with polypharmacology.
基于结构的药物设计如今在现代药物化学中得到广泛应用。结构生物学在药物化学中的应用开创了发现高度选择性配体的“合理药物设计”愿景。然而，后基因组生物学的最新进展表明，多药理学可能是许多药物发挥疗效的必要特性，因此对当前合理药物设计中“一种药物，一个靶点”的假设提出了质疑。通过结合化学信息学和结构生物学的进展，有可能合理设计出具有多药理学特性的下一代混杂药物。
