Maréchal Eric
Unité mixte de recherche 5168 CNRS-CEA-INRA-Université Joseph Fourier, Institut de Recherches en Technologies et Sciences pour le Vivant, 17 avenue des Martyrs, France.
Comb Chem High Throughput Screen. 2008 Sep;11(8):583-6. doi: 10.2174/138620708785739961.
Chemogenomics is the study of the interaction of functional biological systems with exogenous small molecules, or in broader sense the study of the intersection of biological and chemical spaces. Chemogenomics requires expertises in biology, chemistry and computational sciences (bioinformatics, cheminformatics, large scale statistics and machine learning methods) but it is more than the simple apposition of each of these disciplines. Biological entities interacting with small molecules can be isolated proteins or more elaborate systems, from single cells to complete organisms. The biological space is therefore analyzed at various postgenomic levels (genomic, transcriptomic, proteomic or any phenotypic level). The space of small molecules is partially real, corresponding to commercial and academic collections of compounds, and partially virtual, corresponding to the chemical space possibly synthesizable. Synthetic chemistry has developed novel strategies allowing a physical exploration of this universe of possibilities. A major challenge of cheminformatics is to charter the virtual space of small molecules using realistic biological constraints (bioavailability, druggability, structural biological information). Chemogenomics is a descendent of conventional pharmaceutical approaches, since it involves the screening of chemolibraries for their effect on biological targets, and benefits from the advances in the corresponding enabling technologies and the introduction of new biological markers. Screening was originally motivated by the rigorous discovery of new drugs, neglecting and throwing away any molecule that would fail to meet the standards required for a therapeutic treatment. It is now the basis for the discovery of small molecules that might or might not be directly used as drugs, but which have an immense potential for basic research, as probes to explore an increasing number of biological phenomena. Concerns about the environmental impact of chemical industry open new fields of research for chemogenomics.
化学基因组学是研究功能性生物系统与外源性小分子之间的相互作用，从更广泛的意义上讲，是研究生物空间与化学空间的交叉领域。化学基因组学需要生物学、化学和计算科学（生物信息学、化学信息学、大规模统计学和机器学习方法）方面的专业知识，但它不仅仅是这些学科的简单并列。与小分子相互作用的生物实体可以是分离出的蛋白质，也可以是更复杂的系统，从单细胞到完整生物体。因此，在各种后基因组水平（基因组、转录组、蛋白质组或任何表型水平）上对生物空间进行分析。小分子空间部分是真实的，对应于化合物的商业和学术收藏，部分是虚拟的，对应于可能合成的化学空间。合成化学已经开发出新颖的策略，允许对这个可能性的领域进行实际探索。化学信息学的一个主要挑战是利用现实的生物学限制条件（生物利用度、成药性、结构生物学信息）来描绘小分子的虚拟空间。化学基因组学是传统制药方法的衍生物，因为它涉及筛选化学文库以研究其对生物靶点的作用，并受益于相应支撑技术的进步以及新生物标志物的引入。筛选最初的动机是严格发现新药，忽略并丢弃任何不符合治疗药物所需标准的分子。现在，筛选是发现可能直接用作药物或可能不直接用作药物但在基础研究方面具有巨大潜力的小分子的基础，这些小分子可作为探索越来越多生物现象的探针。对化学工业环境影响的关注为化学基因组学开辟了新的研究领域。
