Kluczyk A, Kiyota T, Lazar C, Popek T, Roman G, Konishi Y
National Research Council Canada, Biotechnology Research Institute, 6100 Royalmount Ave., Montréal, QC, H4P 2R2, Canada.
Med Chem. 2006 Mar;2(2):175-89. doi: 10.2174/157340606776056214.
The drug evolution method represents a novel approach towards efficient rational drug design by implementing the drug evolution concept to the creation and development of general chemical libraries with the purpose of allowing the identification of drug candidates with improved odds and lesser costs than the traditional drug design strategies. As another example of successful translation of the biological evolution into chemical evolution, the chimera method comprises the grafting of selected building blocks, identified through a basic search within a drug library, onto the same substitution sites on a rationally chosen scaffold. The method allows the creation of a library containing both drugs and prospective drug candidates without any priorly required knowledge on the pursued disease or molecular target. Two libraries having scaffolds derived from para-aminobenzoic acid and salicylic acid have exemplified the application of the chimera method. The validation of the method has been achieved through the high number of recognized drugs within the library, which exhibit in the same time a wide variety of therapeutic activities and interact with a broad spectrum of molecular targets. The drug-enriched chimera libraries are expected to provide a highly efficient access to novel drug candidates whose unspecified therapeutic effects should be further revealed through high-throughput screening.
药物进化方法代表了一种高效合理药物设计的新方法，它通过将药物进化概念应用于通用化学文库的创建和开发，目的是识别出比传统药物设计策略更具成功几率且成本更低的候选药物。作为生物进化成功转化为化学进化的另一个例子，嵌合体方法包括将通过在药物库中进行基本搜索确定的选定结构单元嫁接到合理选择的支架上的相同取代位点。该方法允许创建一个既包含药物又包含潜在候选药物的文库，而无需事先了解所研究的疾病或分子靶点。两个具有源自对氨基苯甲酸和水杨酸支架的文库例证了嵌合体方法的应用。该方法的验证是通过文库中大量被认可的药物实现的，这些药物同时展现出广泛的治疗活性并与多种分子靶点相互作用。富含药物的嵌合体文库有望为新型候选药物提供高效获取途径，其未明确的治疗效果应通过高通量筛选进一步揭示。
