Fox Jay W, Serrano Solange M T
University of Virginia, Charlottesville, VA 22908-0734, USA.
Curr Pharm Des. 2007;13(28):2927-34. doi: 10.2174/138161207782023739.
Poisons and the toxins found in venomous and poisonous organisms have been the focus of much research over the past 70 years, most of which has been directed at understanding the biochemical and physiological mechanisms by which they elicit their dramatic pathological consequences. Much knowledge has been gained in terms of how poisons and venoms and their composite toxins give rise to the syndromes associated with envenoming and poisoning and in some isolated cases there have been a few such agents promoted for therapeutic use. However, it has only been in the past decade that an explosion of interest has occurred in mining these natural, highly evolved libraries of bioactive toxins and poisons for use in pharmacotherapeutics as drugs or drug leads as well as in diagnostic applications. We ascribe this recent phenomenon to advances in toxinology which have provided investigators with a relatively thorough understanding of the nature of venoms and their biologically active toxins: particularly with regard to the peptidomes and proteomes of venoms. This is in conjunction with our greatly improved understanding of the etiology of many human diseases and the identification of sites of potential therapeutic intervention. In this review we provide an overview of some of the toxins, toxin derivatives or poisons from animal venoms and secretions which are in various stages of development for use as pharmaceuticals or diagnostics in human diseases. As one will recognize, developments in this field suggest that toxinology is now entering a golden age in terms of the identification and use of toxins as potent novel pharmaceuticals.
在过去70年里,有毒生物体内发现的毒素和毒液一直是众多研究的焦点,其中大部分研究旨在了解它们引发严重病理后果的生化和生理机制。在毒药、毒液及其复合毒素如何导致与中毒和毒液中毒相关的综合征方面,我们已经获得了很多知识,在一些个别案例中,已经有少数此类制剂被推广用于治疗。然而,直到过去十年,人们才对从这些天然的、高度进化的生物活性毒素和毒药库中挖掘用于药物治疗的药物或药物先导物以及诊断应用产生了极大的兴趣。我们将这种近期现象归因于毒素学的进展,这些进展使研究人员对毒液及其生物活性毒素的性质有了相对全面的了解:特别是在毒液的肽组和蛋白质组方面。这与我们对许多人类疾病病因的深入理解以及对潜在治疗干预部位的识别相结合。在这篇综述中,我们概述了一些来自动物毒液和分泌物的毒素、毒素衍生物或毒药,它们正处于开发用于人类疾病的药物或诊断试剂的不同阶段。正如人们将会认识到的,该领域的发展表明,就毒素作为强效新型药物的识别和使用而言,毒素学现在正进入一个黄金时代。