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Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication
Acta Pharmaceutica Sinica B ; (6): 498-511, 2020.
Article in En | WPRIM | ID: wpr-792993
Responsible library: WPRO
ABSTRACT
Ricin is a highly toxic type 2 ribosome-inactivating protein (RIP) which is extracted from the seeds of castor beans. Ricin is considered a potential bioterror agent and no effective antidote for ricin exists so far. In this study, by structural modification of a retrograde transport blocker Retro-2, a series of novel compounds were obtained. The primary screen revealed that compound has an improved anti-ricin activity compare to positive control. pre-exposure evaluation in Madin-Darby Canine Kidney (MDCK) cells demonstrated that is a powerful anti-ricin compound with an EC of 41.05 nmol/L against one LC (lethal concentration, 5.56 ng/mL) of ricin. Further studies surprisingly indicated that confers post-exposure activity against ricin intoxication. An study showed that 1 h post-exposure administration of can improve the survival rate as well as delay the death of ricin-intoxicated mice. A drug combination of with monoclonal antibody mAb4C13 rescued mice from one LD (lethal dose) ricin challenge and the survival rate of tested animals is 100%. These results represent, for the first time, indication that small molecule retrograde transport blocker confers both and post-exposure protection against ricin and therefore provides a promising candidate for the development of anti-ricin medicines.
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Full text: 1 Index: WPRIM Language: En Journal: Acta Pharmaceutica Sinica B Year: 2020 Type: Article
Full text: 1 Index: WPRIM Language: En Journal: Acta Pharmaceutica Sinica B Year: 2020 Type: Article