SYNTHETIC SOD/CATALASE MIMICS FOR STROKE

合成 SOD/过氧化氢酶模拟物治疗中风

• 批准号: 2658793
• 负责人: SUSAN DOCTROW
• 金额: $ 9.68万
• 依托单位: EUKARION, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2658793
• 关键词: antioxidants; catalase; chemical property; drug screening /evaluation; enzyme activity; free radical oxygen; laboratory rat; manganese; nerve injury; solubility; stroke; superoxide dismutase; synthetic enzyme

DESCRIPTION (Adapted from applicant's abstract): Stroke is the third leading cause of death in the U.S., affecting at least 500,000 patients annually, and is considered the most common cause of adult disability. Pharmacological intervention has made little, if any, impact on preventing neurological damage once a stroke has occurred. Reactive oxygen species (ROS), which mediate tissue damage in numerous pathologies, have been implicated in the neurological damage resulting from stroke. Eukarion has developed a class of synthetic molecules that are catalytic ROS scavengers, mimicking the endogenous antioxidant enzymes SOD and catalase. One of these compounds, EUK-134, is highly protective in a rodent model for stroke, even when administered three hours after the onset of brain ischemia. This project will investigate the potential therapeutic value of these compounds for stroke. The specific aims are: (1) To characterize the catalytic and chemical properties of the compounds, focusing on those to be tested in vivo; (2) To further characterize the efficacy of EUK-134 with respect to their effectiveness in the stroke model. The overall goal of this Phase I project is to select candidate(s) for future preclinical and clinical development as therapeutic agents for stroke. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述(摘自申请者的摘要)：笔画是第三个 美国头号死因，影响至少50万名患者 每年，被认为是导致成人残疾的最常见原因。 药物干预对预防的影响甚微，如果有的话。 一旦中风发生就会造成神经损伤。活性氧物种 (ROS)在许多病理过程中介导组织损伤，一直以来 与中风导致的神经损伤有关。尤卡里昂有 开发了一类催化ROS的合成分子 清道夫，模仿内源抗氧化酶超氧化物歧化酶和过氧化氢酶。 其中一种化合物EUK-134在啮齿动物模型中具有高度的保护性。 对于中风，即使在大脑发作三个小时后给药 缺血症。这个项目将调查潜在的治疗价值。 这些化合物中的一种治疗中风。具体目标是：(1) 表征化合物的催化和化学性质， 重点放在那些需要在体内测试的；(2)进一步表征 EUK-134对卒中疗效的影响 模特。本一期工程的总体目标是选拔候选人(S) 作为治疗药物的未来临床前和临床开发 卒中。 建议的商业应用：不可用

项目成果

A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin.

• DOI: 10.1038/jid.2012.410
• 发表时间: 2013-04
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Doctrow, Susan R.;Lopez, Argelia;Schock, Ashley M.;Duncan, Nathan E.;Jourdan, Megan M.;Olasz, Edit B.;Moulder, John E.;Fish, Brian L.;Maeder, Marylou;Lazar, Jozef;Lazarova, Zelmira
• 通讯作者: Lazarova, Zelmira

Mitochondrial transporter ATP binding cassette mitochondrial erythroid is a novel gene required for cardiac recovery after ischemia/reperfusion.

• DOI: 10.1161/circulationaha.110.003418
• 发表时间: 2011-08-16
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Liesa M;Luptak I;Qin F;Hyde BB;Sahin E;Siwik DA;Zhu Z;Pimentel DR;Xu XJ;Ruderman NB;Huffman KD;Doctrow SR;Richey L;Colucci WS;Shirihai OS
• 通讯作者: Shirihai OS