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致癌过程的无毒剂来预防或延迟人类癌症。作为战胜癌症的国家努力的一个组成部分，这种方法的优点是显而易见的。已知多种潜在的癌症化学预防剂，其中大多数是在经验基础上发现的。我们组建了一个多学科团队，专注于发现和表征新的癌症化学预防剂，这些药物是天然产物或天然产物衍生物。正如大量先例所证明的那样，陆生植物提供了广泛的化学多样性。一些独特的成分，用于治疗人类疾病，不能预期除了天然产物药物发现的实验过程。从良好表征的膳食和非膳食植物组的体外生物测定开始，其指示抑制致癌作用的主要阶段。活性物质在具有更大生理复杂性的二级测定系统中进行评价，并且那些与这些二级鉴别剂具有活性的物质经受生物测定指导的分级分离。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，并被视为开发的候选物。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，机制和结构-活性关系的评估，以及从该领域的水平到结构和机制定义的具有已证实疗效的化学实体的水平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，这些项目得到两个核心组成部分和一个外部咨询委员会的协助。为了促进利用新发现的药物预防人类癌症，这是该计划项目的长期目标，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都已被证明是有效的，我们预计未来的进展将有增无减。

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.