Mitochondrial complex I (NADH dehydrogenase) x Pfbc1

更新于：2024-11-01

基本信息

关联

项与 Mitochondrial complex I (NADH dehydrogenase) x Pfbc1 相关的药物

GSK-932121

靶点

Mitochondrial complex I (NADH dehydrogenase) x Pfbc1

作用机制

线粒体复合体I（NADH脱氢酶）抑制剂 [+1]

在研机构

GSK Plc

原研机构

GSK Plc

在研适应症

疟疾

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 Mitochondrial complex I (NADH dehydrogenase) x Pfbc1 相关的临床试验

NCT00811356 / Terminated临床1期

A Single-Blind, Placebo-Controlled, Randomized First Time in Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Dose Escalation of GSK932121 in Healthy Adult Subjects

The purpose of this study is to determine if the study drug (antimalarial medication) is safe when given to healthy subjects as a single dose or as repeated doses, to understand the effect of food on single doses of study drug and to determine if the study drug has an effect on other approved medications such as rosiglitazone and rosuvastatin.

开始日期2008-12-11

申办/合作机构

GSK Plc

100 项与 Mitochondrial complex I (NADH dehydrogenase) x Pfbc1 相关的临床结果

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100 项与 Mitochondrial complex I (NADH dehydrogenase) x Pfbc1 相关的转化医学

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0 项与 Mitochondrial complex I (NADH dehydrogenase) x Pfbc1 相关的专利（医药）

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项与 Mitochondrial complex I (NADH dehydrogenase) x Pfbc1 相关的文献（医药）

2004-03-01·Biochemical Journal3区 · 生物学

Alternative quinone substrates and inhibitors of human electron-transfer flavoprotein-ubiquinone oxidoreductase

3区 · 生物学

Article

作者: FRERMAN, Frank E. ; ŠIMKOVIČ, Martin

Electron-transfer flavoprotein (ETF)-ubiquinone (2,3-dimethoxy-5-methyl-1,4-benzoquinone) oxidoreductase (ETF-QO) is a membrane-bound iron–sulphur flavoprotein that participates in an electron-transport pathway between eleven mitochondrial flavoprotein dehydrogenases and the ubiquinone pool. ETF is the intermediate electron carrier between the dehydrogenases and ETF-QO. The steady-state kinetic constants of human ETF-QO were determined with ubiquinone homologues and analogues that contained saturated n-alkyl substituents at the 6 position. These experiments show that optimal substrates contain a ten-carbon-atom side chain, consistent with a preliminary crystal structure that shows that only the first two of ten isoprene units of co-enzyme Q10 (CoQ10) interact with the protein. Derivatives with saturated alkyl side chains are very good substrates, indicating that, unlike other ubiquinone oxidoreductases, there is little preference for the methyl branches or rigidity of the CoQ side chain. Few of the compounds that inhibit ubiquinone oxidoreductases inhibit ETF-QO. Compounds found to act as inhibitors of ETF-QO include 2-n-heptyl-4-hydroxyquinoline N-oxide, a naphthoquinone analogue, 2-(3-methylpentyl)-4,6-dinitrophenol and pentachlorophenol. 2,5-Dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), which inhibits the mitochondrial bc1 complex and the chloroplast b6f complex in redox-dependent fashion, can serve as an electron acceptor for human ETF-QO. The observation of simple Michaelis–Menten kinetic patterns and a single type of quinone-binding site, determined by fluorescence titrations of the protein with DBMIB and 6-(10-bromodecyl)ubiquinone, are consistent with one ubiquinone-binding site per ETF-QO monomer.