Development of sulfanegen for mass cyanide casualties.
Development of sulfanegen for mass cyanide casualties.
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DOI：
10.1111/nyas.13114
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发表时间：
2016-06
影响因子：
5.2
通讯作者：
Logue BA
中科院分区：
文献类型：
--
作者：
Patterson SE;Moeller B;Nagasawa HT;Vince R;Crankshaw DL;Briggs J;Stutelberg MW;Vinnakota CV;Logue BA
氰化物是一种代谢毒物，会抑制氧气形成 ATP 的利用。急性氰化物暴露的后果很严重，会导致意识丧失、心脏和呼吸衰竭、缺氧性脑损伤以及在几分钟到几小时内剂量依赖性死亡。在发生大规模伤亡的情况下，例如工业事故或恐怖袭击，目前可用的氰化物解毒剂会使许多受害者在成功实施医疗对策的短时间内得不到治疗。这种有限的治疗窗反映了静脉注射的限速步骤，这需要时间和训练有素的医务人员。因此，需要能够快速施用于大量人群的速效解毒剂。为了满足这一需求，我们的实验室正在开发 sulfanegen，这是一种潜在的氰化物中毒解毒剂，具有基于 3-巯基丙酮酸硫转移酶 (3-MST) 的新颖机制，用于氰化物解毒。此外，sulfanegen 可以通过肌肉注射快速给药，并在许多动物模型中显示出疗效。以下总结了这种有希望的解毒剂从概念到临床线索的历程。
Cyanide is a metabolic poison that inhibits the utilization of oxygen to form ATP. The consequences of acute cyanide exposure are severe, and result in loss of consciousness, cardiac and respiratory failure, hypoxic brain injury, and dose-dependent death within minutes to hours. In a mass-casualty scenario, such as an industrial accident or terrorist attack, currently available cyanide antidotes would leave many victims untreated in the short time available for successful administration of a medical countermeasure. This restricted therapeutic window reflects the rate-limiting step of intravenous administration, which requires both time and trained medical personnel. Therefore, there is a need for rapidly acting antidotes that can be quickly administered to large numbers of people. To meet this need, our lab is developing sulfanegen, a potential antidote for cyanide poisoning with a novel mechanism based on 3-mercaptopyruvate sulfurtransferase (3-MST) for the detoxification of cyanide. Additionally, sulfanegen can be rapidly administered by intramuscular injection and has shown efficacy in many species of animal models. The following summarizes the journey from concept to clinical leads for this promising antidote.