Neidle Stephen, Thurston David E
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Discov Med. 2005 Oct;5(29):450-4.
Extract: The chemical sciences are increasingly overlapping with many aspects of the study of biological molecules at the molecular level. By contrast, the traditional view of chemistry, at least as far as cancer therapeutics is concerned, has been a much narrower one as a tool of the cancer drug discovery process, generally being solely concerned with synthesis. The thesis that we develop in this short review is that the role of the chemical sciences in cancer therapeutics increasingly covers far more than this, and requires the active involvement of many aspects of the subject if the full potential of our knowledge of the cellular, molecular, and genetic basis of cancer is to be translated into clinically useful therapeutics. Effective drug discovery requires an understanding of small molecule and macromolecule physico-chemical properties, mechanism of action, structure and reactivity of individual components (including targets) of pathways, and the ways in which they interact together by means of both covalent and non-covalent recognition and signal transfer. It is no coincidence that several effective clinical agents have been discovered by creative chemists who possess a deep understanding of these topics, especially of the relationships between the structure and reactivity properties of a particular class of molecules, leading to insights into their potential as anticancer agents.
化学科学在分子水平上与生物分子研究的许多方面越来越相互重叠。相比之下,至少就癌症治疗而言,化学的传统观点一直更为狭隘,仅仅是癌症药物发现过程中的一种工具,通常只涉及合成。我们在这篇简短综述中提出的论点是,化学科学在癌症治疗中的作用越来越远超于此,如果要将我们对癌症细胞、分子和遗传基础的全部知识潜力转化为临床可用的治疗方法,就需要该学科多个方面的积极参与。有效的药物发现需要了解小分子和大分子的物理化学性质、作用机制、途径中各个组分(包括靶点)的结构和反应性,以及它们通过共价和非共价识别与信号转导相互作用的方式。一些有创意的化学家发现了几种有效的临床药物,这些化学家对这些主题有深刻的理解,尤其是对特定一类分子的结构和反应性性质之间的关系有深刻理解,从而洞察了它们作为抗癌药物的潜力,这并非巧合。