Laboratory of Molecular Toxinology and Biotechnology, Molecular engineering of proteins (SIMOPRO), Life Sciences Division (DSV), Institute of Biology and Technology Saclay, French Alternative Energies and Atomic Energy Commission (CEA), F-91191 Gif sur Yvette, France.
Toxins (Basel). 2012 Jan;4(1):15-27. doi: 10.3390/toxins4010015. Epub 2012 Jan 6.
Throughout the last decade, efforts to identify and develop effective inhibitors of the ricin toxin have focused on targeting its N-glycosidase activity. Alternatively, molecules disrupting intracellular trafficking have been shown to block ricin toxicity. Several research teams have recently developed high-throughput phenotypic screens for small molecules acting on the intracellular targets required for entry of ricin into cells. These screens have identified inhibitory compounds that can protect cells, and sometimes even animals against ricin. We review these newly discovered cellular inhibitors of ricin intoxication, discuss the advantages and drawbacks of chemical-genetics approaches, and address the issues to be resolved so that the therapeutic development of these small-molecule compounds can progress.
在过去的十年中，人们致力于鉴定和开发有效的蓖麻毒素抑制剂，主要集中在针对其 N-糖苷酶活性上。此外，破坏细胞内运输的分子已被证明可以阻止蓖麻毒素的毒性。最近，几个研究小组已经开发了针对进入细胞所需的细胞内靶标的小分子的高通量表型筛选。这些筛选已经鉴定出能够保护细胞甚至动物免受蓖麻毒素侵害的抑制化合物。我们综述了这些新发现的细胞内蓖麻毒素中毒抑制剂，讨论了化学遗传学方法的优缺点，并解决了需要解决的问题，以便这些小分子化合物的治疗开发能够取得进展。
