NATURAL INHIBITORS OF CARCINOGENESIS

化学预防是一种治疗方法，其中通过口服能够抑制癌变过程的无毒药剂来预防或延缓人类癌症。作为国家战胜癌症努力的一个组成部分，这种方法的优点是显而易见的。各种潜在的癌症化学预防剂是已知的，其中大多数是在经验基础上发现的。我们已经组建了一个多学科的团队，专注于发现和表征新的癌症化学预防剂，这些化学预防剂是天然产物或天然产物衍生物。有充分的先例证明，陆生植物具有广泛的化学多样性。一些对治疗人类疾病有用的独特成分，除了天然产物药物发现的实验过程之外，是无法预料的。从具有良好特征的饮食和非饮食植物组开始，体外生物测定表明抑制主要阶段的致癌作用。活性物质在生理更复杂的二级分析系统中进行评估，那些具有这些二级鉴别器的活性物质受到生物测定引导的分离。活性成分通过物理和光谱方法进行结构定义，在更广泛的生物测定系统中进行评估，并被认为是开发的候选物质。作为该计划项目的一部分，开发涉及化学合成或大规模分离，机制和构效关系的评估，以及从领域层面到结构和机制层面确定的已证实治疗效果的化学实体的短期或长期癌症化学预防潜力的建立。这些工作需要五个独立项目的努力，并得到两个核心组成部分和一个外部咨询委员会的协助。为了促进新发现的药物在预防人类癌症方面的应用，这是该项目的长期目标，我们与孟山都生命科学公司建立了正式的合作伙伴关系。该计划项目的所有要素已被证明是有效的，我们预计未来将取得有增无减的进展。

Chemoprevention is a therapeutic method wherein human cancer is prevented or delayed through oral consumption of non-toxic agents capable of inhibiting the process of carcinogenesis. As an integral component of the national effort to defeat cancer, the merit of this approach is intuitively obvious. A variety of potential cancer chemopreventive agents are known, most of which were discovered on an empirical basis. We have assembled a multi-disciplinary team focused on the discovery and characterization of new cancer chemopreventive agents that are natural products or natural product derivatives. As established by ample precedent, terrestrial plants provide broad chemical diversity. Some unique constituents, useful for the treatment of human ailments, cannot be anticipated aside from the experimental process of natural product drug discovery. Starting with well-characterized dietary and non- dietary plant panel of in vitro bioassays indicative of inhibiting major stages of carcinogenesis. Active materials are evaluated in secondary assay systems of greater physiologic complexity, and those active with these secondary discriminators are subjected to bioassay-guided fractionation. Active principles are structurally-defined by physical and spectroscopic methods, evaluated in a broader array of bioassay systems, and considered as candidates for development. As part of this program project, development involves chemical synthesis or large-scale isolation, evaluation of mechanism and structure-activity relationships, and establishment of cancer chemopreventive potential in short- or long-term from the level of the field to the level of structurally- and mechanistically- defined chemical entities of proven therapeutic efficacy. These undertakings require the efforts of five separate projects that are assisted by two core components, and an External Advisory Board. To facilitate utilization of the newly discovered agents for the prevention of human cancers, the long-term objective of this program project, a formal partnership has been instituted with Monsanto Life Sciences. All elements of the program project have proven effective, and we anticipate unabated progress in the future.