生物活性

• 描述FCCP is a potent mitochondrial oxidative phosphorylation uncoupler which exhibits uncoupling effects at concentrations down to 10 ^-8 molar in mouse liver mitochondria^[1]. Treatment with 5μM FCCP led to a reduction of ATP levels and ROS production and stimulated mitochondrial biogenesis related genes including Pgc-1α, mitochondrial genes such as Tfam and COXIV in hepatic stellate cells^[2]. FCCP at concentration of 62.5nM and 125nM significantly reduced the mitochondrial membrane potential in the cytoplasmic and cortical region, as well as decreased ATP level of 8-cell embryos^[3]. The processing of mutant APP in K695sw cells and wild-type APP in K695 cells was inhibited post treatment with 5μM FCCP for 4h^[4].
• 作用机制FCCP is a protonophore which can induce ionic currents carried by Na⁺ and H⁺ and depolarization dependent on the plasmalemmal proton gradient.^[5]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  Hep3B cells	10 μM	Function assay	-	Stimulation of state 4 cellular respiration in human Hep3B cells at 10 uM in presence of oligomycin	22938093
  MDA-MB-231 cells	1 uM	Cytotoxicity assay	-	Cytotoxicity against human MDA-MB-231 cells assessed as inhibition of cell proliferation/viability at 1 uM	23245650
  SH-SY5Y cells	10 μM	Function assay	10 mins	Induction of mitochondrial membrane potential loss in human SH-SY5Y cells at 10 uM incubated for 10 mins in presence of 0.2 uM CsA by TMRE dye based assay	25265024

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• 动物研究
  剂量	Rat: 0.5 mg/kg - 5 mg/kg[6] (i.p.); 1.5 mg/kg - 2.5 mg/kg[7] (s.c.)
  给药途径	i.p., s.c.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00613860	Emphysema COP... more >>D Collapse <<	Phase 3	Unknown	December 2011	Germany ... more >> Charite, University of Berlin Recruiting Berlin, Germany, 10117 Contact: Christian Witt, MD, PhD    +49 (030) 450 565 022    pneumologie@charite.de    Contact: Bernd Schmitt, MD    +49 (030) 450 565 02    pneumologie@charite.de    Thoraxklinik, University of Heidelberg Recruiting Heidelberg, Germany, 69190 Principal Investigator: Felix JF Herth, MD, PhD          Medical Center Nürnberg Recruiting Nürnberg, Germany, 90340 Contact: Joachim Ficker, MD, PHD    +49 (911) 398-2675    ficker@klinikum-nuernberg.de    Contact: Manfred Wagner, MD    +49 (911) 398-0    Manfred.Wagner@klinikum-nuernberg.de Collapse <<
  NCT00176540	Fatigue Unspe... more >>cified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific Collapse <<	Not Applicable	Terminated(slow accrual)	-	United States, New Jersey ... more >> Cancer Institute of New Jersey at Hamilton Hamilton, New Jersey, United States, 08690 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey, United States, 08903 Collapse <<
  NCT01187147	Asthma	Not Applicable	Completed	-	Hong Kong ... more >> University of Hong Kong Queen Mary Hospital Hong Kong, Hong Kong, 0 Collapse <<

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• 参考文献

• [1] HEYTLER PG, PRICHARD WW, et al. A new class of uncoupling agents--carbonyl cyanide phenylhydrazones. Biochem Biophys Res Commun. 1962 May 4;7:272-5.

  [2] Guimarães EL, Best J, et al. Mitochondrial uncouplers inhibit hepatic stellate cell activation. BMC Gastroenterol. 2012 Jun 11;12:68.

  [3] Zander-Fox DL, Fullston T, et al. Reduction of Mitochondrial Function by FCCP During Mouse Cleavage Stage Embryo Culture Reduces Birth Weight and Impairs the Metabolic Health of Offspring. Biol Reprod. 2015 May;92(5):124.

  [4] Connop BP, Thies RL, et al. Novel effects of FCCP [carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone] on amyloid precursor protein processing. J Neurochem. 1999 Apr;72(4):1457-65.

  [5] Park KS, Jo I, et al. FCCP depolarizes plasma membrane potential by activating proton and Na+ currents in bovine aortic endothelial cells. Pflugers Arch. 2002 Jan;443(3):344-52. Epub 2001 Oct 6.

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